Category Archives: Transhuman News

Weve all heard the conspiracy theories about COVID-19. Now a whole new set is emerging around COVID vaccines and spreading as virulently as the pandemic they are meant to control.

Though the public health community tends to resort to reassurances about some of the more reasonable concerns yes, the vaccines have been developed incredibly quickly and short-term side effects can occur this post aims to do something different.

Were going right to the heart of the matter. So no, COVID-19 vaccines arent delivery vehicles for government microchips. They arent tainted by material from aborted fetuses. And they wont turn us into GMOs though some of them do use genetic engineering, and all of them use genetics more broadly.

We think this is way cool something to celebrate, not shy away from. So, were doing the deep reveal on exactly how genetics and biotechnology have been a central component of the vaccine effort. Because we know the conspiracists dont care about evidence, anyway.

First up: mRNA. It wont reprogram your brain. But it does reprogram some of your cells, in a manner of speaking. And thats not a defect its intentional.

To get your head around this you need to understand what mRNA is for. Basically, its a single-stranded nucleic acid molecule that carries a genetic sequence from the DNA in the cells nucleus into the protein factories called ribosomes that sit outside the nucleus in the cellular cytoplasm.

Thats what the m in mRNA stands for: messenger. Messenger RNA just carries instructions for the assembly of proteins from the DNA template to the ribosomes. (Proteins do almost everything that matters in the body.) Thats it.

This is useful for vaccines because scientists can easily reconstruct specific genetic sequences that encode for proteins that are unique to the invading virus. In the COVID case, this is the familiar spike protein that enables the coronavirus to enter human cells.

What mRNA vaccines do is prompt a few of your cells near the injection site to produce the spike protein. This then primes your immune system to build the antibodies and T-cells that will fight off the real coronavirus infection when it comes.

Its not hugely different from how traditional vaccines work. But instead of injecting a weakened live or killed virus, the mRNA approach trains your immune system directly with a single protein.

Contrary to assertions made by opponents, it wont turn you or anyone else into a GMO. mRNA stays in the cytoplasm, where the ribosomes are. It does not enter the nucleus and cannot interact with your DNA or cause any changes to the genome. No Frankencure here, either.

A variant of the mRNA approach is to go one step back in the process and construct a vaccine platform out of DNA instead. This DNA template constructed by scientists to encode for the coronavirus spike protein gets into cells where it is read into mRNA and well the rest is the same.

You might ask whether this DNA can genetically engineer your cells. Once again, the answer is no. DNA is injected in little circular pieces called plasmids not to be confused with plastics and while these do enter the nucleus, the new DNA does not integrate into your cellular genome. Got it?

This one really is genetically engineered. But what does that actually mean?

The Oxford vaccine uses what is called a viral vector approach. The scientific team took an adenovirus a type of pathogen that causes a common cold and spliced in the same spike protein genetic sequence from the coronavirus.

The adenovirus simply serves as the vehicle to get the genetic sequence into your cells. Thats why its called a viral vector after all. Viruses have been designed by billions of years of evolution precisely to figure out ways to sneak into host cells.

Note that genetic engineering is an essential part of the development process. Firstly, vector viruses are stripped of any genes that might harm you and actually cause disease. Genes that cause replication are also removed, so the virus is harmless and cannot replicate.

Then the coronavirus spike protein genes are added a classic use of recombinant DNA. So yes, the Oxford/AstraZeneca vaccine does actually mean a genetically engineered virus is injected into your body.

And thats a good thing. In the past, for example with the polio vaccine, live viruses in the vaccine can sometimes mutate and revert to being pathogenic, causing vaccine-derived polio. You can see its far better to use a GM virus that cannot cause any such harm!

As we have reported before at the Alliance for Science, the anti-GMO and anti-vaccine movements substantially overlap. These groups tend to share an ideology that is suspicious of modern science and fetishsize natural approaches instead. Whatever natural means.

Note that these groups are not always marginalized to the fringe where they belong. In Europe, anti-GMO regulations have stymied any substantial use of crop biotechnology for nearly two decades, hindering efforts to to make agriculture more sustainable.

And back in July, the European Parliament actually had to suspend the EUs anti-GMO rules in order to allow the unimpeded development of COVID vaccines. Very embarrassing for Brussels!

Will the anti-GMO and anti-vaxxer movements use their usual scaremongering tactics to drum up fear, increase vaccine hesitancy and thereby prolong the hell of the COVID-19 pandemic? That remains to be seen. If they do succeed, then tragically many more people will die and our economies will continue to suffer. Its up to all of us the grassroots pro-science movement to stop them.

Image: Coronavirus and DNA strands. Medical 3D illustration by peterschreiber.media/Shutterstock.

Originally posted here:
Yes, some COVID vaccines use genetic engineering. Get over ...

Across the Florida Keys this week, newly hatched mosquitoes are swarming from damp flowerpots, waterlogged spare tires, trash cans and drainage ditches. In six neighborhoods, however, a change is buzzing in the air. Scientists have genetically modified thousands of these mosquitoes and, for the first time in the U.S., set them free to breed.

These genetically engineered insects, known by their model number as OX5034, are a laboratory offshoot of the Aedes aegypti mosquito that transmits dengue, Zika and other infectious ills. After a decade of public debate and regulatory delays, these insects are being released by a U.K. biotechnology company called Oxitec.

Using genetic-engineering techniques, the company altered the male mosquitoes to pass down a gene that makes females need a dash of the antibiotic tetracycline to survive. Without it, females that spread the disease die as larvae. Altered males, which dont bite, seek out wild females to mate and spread the lethal trait to future generations. Gradually, more females die. The swarms dwindle and disappear, with no need for chemical insecticides.

The Florida Keys field trial is a key step toward federal product approval for the altered insects from the U.S. Environmental Protection Agency, which granted the company an experimental use permit for the test. This is a big deal, says molecular biologist Anthony James at the University of California, Irvine, who develops bioengineered mosquitoes but is not involved in the project.

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Genetically Altered Mosquitoes Target Deadly Dengue Fever and Zika - The Wall Street Journal

By Jeremy Schwartz, CFA, Global Head of Research;Kara Marciscano, CFA, Associate, Research

If the 19th century was the century of chemistry and the 20th the century of physics, the 21st will be the century of biology. Jamie Metzl

Revolutionary advances across multiple fields including computer science, artificial intelligence, big data analytics, automation, chemistry, biology and engineering are creating previously unimaginable new opportunities to reengineer biological systems in ways that will revolutionize health care, agriculture, manufacturing, energy production, consumer services and data storage.

The revolution in our ability to read, understand, write and hack DNA, the genetic code of all life, will touch most aspects of how we live.

All organisms have their own genome, a complete set of DNA that contains instructions to develop and direct the activities of life.

Researchers can sequence DNA (determine the order and information carried in DNA) more rapidly and cost-effectively than ever before, which is driving transformations in health care and many other sectors of our global economy.

The development of Modernas COVID-19 vaccine is just one poignant exampleit took the company only two days to design the sequence for its mRNA vaccine!1

We believe the biology revolution is creating a historic investment opportunity equivalent to the industrial and internet revolutions, and theWisdomTree BioRevolution Fund (WDNA)may be uniquely positioned to capture the companies at the intersection of science, technology and engineering.

WDNA seeks to track the price and yield performance, before fees and expenses, of theWisdomTree BioRevolution Index (WTDNA), which provides targeted exposure to companies that we believe lead the transformations and advancements in genetics and biotechnology.

To construct the WisdomTree BioRevolution Index, we leverage data from leading technology futurist2Dr. Jamie Metzl as a third-party consultant. Recognized as a thought leader on the biology revolution, Dr. Metzl authored Hacking Darwin: Genetic Engineering and the Future of Humanity, and he serves as a member of the World Health Organizations expert committee on human genome editing.

Considering proprietary data from Dr. Metzl, WTDNA identifies the key sectors and industry verticals that are expected to be most significantly transformed by advances in biological science and technology, as well as the companies that WisdomTree believes are most representative of this wave of innovation.

The technologies underpinning the biology revolution are connected and reinforce advancements across interdisciplinary fields. We have identified four key BioRevolution sectors, each including multiple subsectors of impact.

Human Health The genetics and biotechnology revolutions are most often associated with health care because many of the most high-profile preliminary applications are health care related. The quantity and quality of these applications will increase significantly as our health care systems transition from generalized medicine based on population averages to personalized, or precision, health care based on each persons individual biology. When the amount of data collected on the human genome reaches critical mass, our system will transition to a predictive and preventive health care system that will help us live healthier and longer lives.

Although health care is the most mature market to date, we expect other sectors to catch up.

Agriculture & Food Technologies will supercharge the selective breeding process to accomplish in months or a few years what previously might have taken centuries or millennia. Pest resistance, yield and variety can be enhanced significantly for staple crops, which can also be engineered to significantly increase photosynthesis to slow climate change. Domesticated animals can be engineered to increase disease resistance, productivity and product quality through marker-assisted selective breeding targeting specific desired outcomes.

Materials Chemicals & Energy The sourcing of industrial inputs for manufacturing is another area ripe for transformation. As the human population grows toward an estimated 10 billion people by mid-century, current resource extraction models will not be sustainable. The tools of the genetics and biotechnology revolutions, however, are making it possible to create materials at scale by manipulating genetic code rather than extracting them from nature. Instead of making plastic from petroleum and fragrances from flowers, for example, we can produce both through the genetic engineering of yeast and other microbes.

Biological Machines & Interfaces Connection and communication between the biology of humans and computers, including the use of DNA for computing and storage, is increasing the potential to extract, store and process data from individuals.

WTDNA currently holds approximately 80% of its weight within the Human Health sector. Over time, we expect the maturation of Agriculture & Food as well as Materials, Chemicals & Energy to drive their increased representation in WTDNA.

Although the general direction and accelerating pace of this revolution are nearly certain, the time horizons for how each specific application will play out will vary. Our approach targets dynamic companies deploying revolutionary technologies both in and outside of health care, and it invests in a wide range of 115 companies across the BioRevolution impact spectrum to reduce single-stock concentration risk.

We believe the diverse portfolio of companies captured in WDNA is the best way for investors to gain exposure to the biology revolution that we expect to fundamentally transform our world and lives over the coming years.

Originally published by WisdomTree, 6/3/21

1As of 5/25/21, WTDNA held 0.6% of its weight in Moderna.2An individual who studies or predicts the future based on current trends in technology

Important Risks Related to this Article

There are risks associated with investing, including possible loss of principal. The Fund invests in BioRevolution companies, which are companies significantly transformed by advancements in genetics and biotechnology. BioRevolution companies face intense competition and potentially rapid product obsolescence. These companies may be adversely affected by the loss or impairment of intellectual property rights and other proprietary information or changes in government regulations or policies. Additionally, BioRevolution companies may be subject to risks associated with genetic analysis. The Fund invests in the securities included in, or representative of, its Index regardless of their investment merit, and the Fund does not attempt to outperform its Index or take defensive positions in declining markets. The composition of the Index is governed by an Index Committee, and the Index may not perform as intended. Please read the Funds prospectus for specific details regarding the Funds risk profile.

U.S. investors only: Clickhereto obtain a WisdomTree ETF prospectus which contains investment objectives, risks, charges, expenses, and other information; read and consider carefully before investing.

There are risks involved with investing, including possible loss of principal. Foreign investing involves currency, political and economic risk. Funds focusing on a single country, sector and/or funds that emphasize investments in smaller companies may experience greater price volatility. Investments in emerging markets, currency, fixed income and alternative investments include additional risks. Please see prospectus for discussion of risks.

Past performance is not indicative of future results. This material contains the opinions of the author, which are subject to change, and should not to be considered or interpreted as a recommendation to participate in any particular trading strategy, or deemed to be an offer or sale of any investment product and it should not be relied on as such. There is no guarantee that any strategies discussed will work under all market conditions. This material represents an assessment of the market environment at a specific time and is not intended to be a forecast of future events or a guarantee of future results. This material should not be relied upon as research or investment advice regarding any security in particular. The user of this information assumes the entire risk of any use made of the information provided herein. Neither WisdomTree nor its affiliates, nor Foreside Fund Services, LLC, or its affiliates provide tax or legal advice. Investors seeking tax or legal advice should consult their tax or legal advisor. Unless expressly stated otherwise the opinions, interpretations or findings expressed herein do not necessarily represent the views of WisdomTree or any of its affiliates.

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Gaining Exposure to the BioRevolution Megatrend - ETF Trends

Scientists have developed a synthetic strain of Escherichia coli that can construct artificial polymers from building blocks that are not found in nature, by following instructions that the researchers encoded in their genes. The scientists, led by a team at the Medical Research Council (MRC) Laboratory of Molecular Biology, engineered the genetic code of the E. coli strain to include several nonstandard amino acids, and found that this synthetic genome made the bacteria entirely resistant to infection by viruses.

The work is some of the first to design proteins that incorporate multiple non-canonical amino acids. The team suggests that their work, and achievement could lead to the development of new polymers such as proteins and plastics, and drugs including antibiotics, as well as making it easier to manufacture drugs reliably using bacteria.

The newly reported achievement builds on previous ground-breaking work by researchers who, in 2019, developed a new techniques to create the biggest ever synthetic genomeconstructing the entire E. coli genome from scratch. Commenting on the latest developments, study lead, Jason Chin, PhD, from the MRC Laboratory of Molecular Biology, said, These bacteria may be turned into renewable and programmable factories that produce a wide range of new molecules with novel properties, which could have benefits for biotechnology and medicine, including making new drugs, such as new antibiotics.

The investigators report on their latest development in Science, in a paper titled, Sense codon reassignment enables viral resistance and encoded polymer synthesis.

The genetic code instructs a cell how to make proteins, which are constructed by joining together strings of natural (canonical) amino acid building blocks. The genetic code in DNA is made up of four bases, represented by the letters: A, T, C and G. When a peptide or protein is being constructed, the four letters in DNA are read in groups of three letters, or codonsfor example TCG. Each codon tells the cell to add a specific amino acid to the peptide chain, which it does via molecules called transfer RNA (tRNA). Each codon is recognized by a specific tRNA, which then adds the corresponding amino acid. For example, the tRNA that recognizes the codon TCG, brings the amino acid serine.

With four letters in groups of three, there are 64 possible combinations of letters, but there are only 20 different canonical amino acids that cells commonly use. So, several different codons can be synonymousthey all code for the same amino acid for example, TCG, TCA, AGC and AGT all code for serine. There are also codons which tell a cell when to stop making a protein, such as TAG and TAA.

Its thought that removing certain codons and the transfer RNAs that read them from the genome and replacing them with noncanonical amino acids (ncAAs) may enable the creation of synthetic cells with properties not found in natural biology, including powerful viral resistances and enhanced biosynthesis of novel proteins. However, these hypotheses have not been experimentally tested, the authors wrote. And to date, the approach has been largely restricted to the incorporation of a single ncAA into a polypeptide chain. As the team noted, limitations preclude the synthesis of noncanonical heteropolymer sequences composed entirely of noncanonical monomers.

In 2019, the team at the MRC Laboratory of Molecular Biology created the first entire genome synthesized from scratch for the commonly studied bacteria, E. coli. They also took the opportunity to simplify its genome. In this engineered strain the scientists replaced some of the codons with their synonyms. So, they removed every instance of TCG and TCA and replaced them with the synonyms AGC and AGT. They also removed every instance of the stop codon TAG and replaced it with its synonym TAA. This meant that the modified bacteria no longer had the codons TCG, TCA and TAG in their genome, but they could still make normal proteins and live and grow.

The MRC scientists goal was to utilize their new technology to create the first cell that can assemble polymers entirely from building blocks that are not found in nature. For the newly reported studies, the scientists further modified the bacteria to remove the tRNA molecules that recognize the codons TCG and TCA. This means that, even if there are TCG or TCA codons in the genetic code, the cell no longer has the molecule that can read those codons.

This is fatal for any virus that tries to infect the cell, because viruses replicate by injecting their genome into a cell and hijacking the cells machinery. Virus genomes still contain lots of the TCG, TCA and TAG codons, but the modified bacteria are missing the tRNAs to read these codons. So when the machinery in the modified bacteria tries to read the virus genome, it fails every time it reaches a TCG, TCA or TAG codon.

When the researchers infected their bacteria with a cocktail of viruses, they confirmed that while unmodified, control bacteria were killed by these pathogens, the modified bacteria were resistant to infection and survived.

Many drugsfor example, protein drugs, such as insulin, and polysaccharide and protein subunit vaccinesare manufactured by growing bacteria that contain instructions to produce the drug. So making bacteria that are resistant to viruses could make manufacturing certain types of drugs more reliable and cheaper. Chin explained, If a virus gets into the vats of bacteria used to manufacture certain drugs then it can destroy the whole batch. Our modified bacterial cells could overcome this problem by being completely resistant to viruses. Because viruses use the full genetic code, the modified bacteria wont be able to read the viral genes. The team further wrote, We have synthetically uncoupled our strain from the ability to read the canonical code, and this advance provides a potential basis for bioproduction without the catastrophic risks associated with viral contamination and lysis.

By creating bacteria with synthetic genomes that do not use certain codons, the researchers also effectively freed up those codons to be used for other purposes, such as coding for synthetic building blocks (monomers). We reassigned these codons to enable the efficient synthesis of proteins containing three distinct noncanonical amino acids, the authors explained. For the studies detailed in Science, the team engineered the bacteria to produce tRNAs coupled with artificial monomers, which recognized the newly available codons (TCG and TAG).

They inserted genetic sequences with strings of TCG and TAG codons into the bacterias DNA. These were read by the altered tRNAs, which assembled chains of synthetic monomers in the sequence defined by the sequence of codons in the DNA. The cells were programmed to string together monomers in different orders by changing the order of TCG and TAG codons in the genetic sequence. Polymers composed of different monomers were also made by changing which monomers were coupled to the tRNAs. We incorporated three distinct ncAAs into ubiquitin, in response to TCG, TCA, and TAG, the team explained. We demonstrated the generality of our approach by synthesizing seven distinct versions of ubiquitin, each of which incorporated three distinct ncAAs.

Using their approach the scientists were able to create polymers made of up to eight monomers strung together. They joined the ends of these polymers together to make macrocyclesa type of molecule that forms the basis of some drugs, such as certain antibiotics and cancer drugs.

Chin said, This system allows us to write a gene that encodes the instructions to make polymers out of monomers that dont occur in nature. Wed like to use these bacteria to discover and build long synthetic polymers that fold up into structures and may form new classes of materials and medicines. We will also investigate applications of this technology to develop novel polymers, such as biodegradable plastics, which could contribute to a circular bioeconomy.

The synthetic monomers were linked together by the same chemical bonds that join together amino acids in proteins, but the researchers are in addition investigating how to expand the range of linkages that can be used in the new polymers. In their paper, they concluded, Future work will expand the principles we have exemplified herein to further compress and reassign the genetic code. We anticipate that, in combination with ongoing advances in engineering the translational machinery of cells, this work will enable the programmable and encoded cellular synthesis of an expanded set of noncanonical heteropolymers with emergent, and potentially useful, properties.

Commenting in an accompanying Perspective in the same issue of Science, D. Jewel, and A. Chatterjee, from Boston College in Chestnut Hill, acknowledged, The ability to generate designer proteins using multiple non-natural building blocks will unlock countless applications, from the development of new classes of biotherapeutics to biomaterials with innovative properties.

Megan Dowie, PhD, head of molecular and cellular medicine at the MRC, which funded the study, said, Dr. Chins pioneering work into genetic code expansion is a really exciting example of the value of our long-term commitment to discovery science. Research like this, in synthetic and engineering biology, clearly has huge potential for major impact in biopharma and other industrial settings.

Go here to read the rest:
Synthetic E. Coli Reprogrammed to Make Polymers from Artificial Monomers, and Resist Viral Infections - Genetic Engineering & Biotechnology News

In the second part of our whats exciting the experts series, Medical News Today spoke with another group of cancer experts. We asked them what recent advances have given them the most hope. Here, we provide a sneak peek at the fascinating forefront of cancer research in 2021.

Cancer is not a single disease but a collection of diseases. It is complex and does not readily give up its secrets. Despite the challenges cancer poses, scientists and clinicians continue to hone the way in which they diagnose and treat it.

Modern medicine means that diagnosis rates for many cancers are up, as are survival rates. However, with an estimated 19.3 million new cases of cancer worldwide in 2020, there is still much work to be done.

MNT recently contacted a number of medical experts and researchers and asked them to speak about the aspects of cancer research that they find most exciting. Their answers are fascinating and demonstrate the incredible variety of approaches that scientists are using to understand and combat cancer.

We will start todays journey into cutting edge oncology with a surprising guest: magnetically responsive bacteria.

Due to the difficulty of targeting systemically delivered therapeutics for cancer, interest has grown in exploiting biological agents to enhance tumor accumulation, explained Prof. Simone Schrle-Finke, Ph.D., from ETH Zurich in Switzerland.

In other words, getting cancer drugs to the right place is not as straightforward as one might hope. Prof. Schrle-Finke is among the researchers who are now enlisting the help of specialized bacteria.

She told MNT how scientists have known for a century that certain bacteria can colonize tumors and trigger regression. She explained that today, thanks to modern genetic engineering techniques, attenuated bacteria are available that can have a therapeutic effect exactly where this is necessary.

These therapeutic effects include secretion of toxins, competition for nutrients, and modulation of immune responses.

However, despite the promise of bacterial cancer therapy, there are still challenges to meet. Delivering the doses to the right place and getting them into the tumor remain foremost among challenges hampering clinical translation only about 1% of a systemically injected dose reaches the tumor, explained Prof. Schrle-Finke.

To address these challenges, her team at ETH Zurich is using magnetically responsive bacteria.

These so-called magnetotactic bacteria naturally orient themselves like compass needles to Earths magnetic field.

Although this ability evolved for navigation, scientists are keen to find out whether magnetic steering or pulling could allow them to repurpose it for cancer delivery.

In a recent study, Prof. Schrle-Finke and her colleagues used rotating magnetic fields to override the bacterias natural propulsion. As the authors of the study explain, they used swarms of magnetotactic bacteria to create a directable living ferrofluid.

These magnetotactic bacteria have a high demand for iron, so once they reach the tumor, as Prof. Schrle-Finke told MNT, they can metabolically influence cancer cells through starvation from this vital nutrient. We have shown in in vitro models that an increasing number of bacteria induce an upregulation of iron-scavenging receptors and death in cancer cells.

By uniting engineering principles and synthetic biology, we aim to provide a new framework for bacterial cancer therapy that addresses a major remaining hurdle by improving the efficiency of bacterial delivery using safe and scalable magnetic stimuli to these promising living therapeutic platforms.

Prof. Simone Schrle-Finke, Ph.D.

Personalized medicine is transforming the landscape of medicine and how healthcare providers can offer and plan personalized care for each of their patients, believes Dr. Santosh Kesari, Ph.D., director of neuro-oncology at Providence Saint Johns Health Center in Santa Monica, CA.

Dr. Kesari is also chair of the Department of Translational Neurosciences at Saint Johns Cancer Institute and regional medical director for the Research Clinical Institute of Providence Southern California.

Describing personalized medicine, Dr. Kesari said, It is an approach for disease prevention and treatment that takes into account biological, genetic, behavioral, environmental, and social risk factors that are unique to every individual.

He continued, Personalized medicine is rooted in early detection and prevention; integrating data from genomics and other advanced technologies; digital health monitoring; and incorporating the latest medical innovations for optimizing outcomes.

This is becoming very apparent in oncology, where genetic testing for tumor mutations and predispositions is increasingly being utilized and showing more value in using targeted drugs more wisely and improving outcomes.

Dr. Santosh Kesari, Ph.D.

Some personalized cancer approaches are already in use, such as EGFR, HER2, and NTRK inhibitors and the super personalized CAR-T cells.

According to Dr. Kesari, the future of personalization is bright, and progress has only accelerated in the past 5 years.

Continuing with the personalization theme, Dr. Robert Dallmann from Warwick Medical School at Warwick University in the United Kingdom talked with us about chronotherapy:

Propelled by the 2017 Nobel Prize in Medicine or Physiology [going] to three circadian biologists for uncovering the molecular mechanism of circadian biological clocks, cancer chronotherapy is gaining critical momentum to enter mainstream oncology especially in the context of personalized medicine.

Dr. Dallmann explained that many key physiological processes in the cells of our body are modulated in a daily fashion by the circadian clock. These cellular clocks are disrupted in some tumors but not in others.

Interestingly, a functional clock in the tumor predicts the survival time of patients, which has been shown for brain as well as breast tumors.

Therefore, he explained, if scientists could determine the clock status in solid tumors, it would allow doctors to more easily determine whether a patient is at high or low risk. It might also help guide therapy.

There is great potential in optimizing treatment plans with existing drugs by taking into account the interaction with the circadian system of the patient, continued Dr. Dallmann.

More recently, the circadian clock mechanism itself has been proposed as a novel treatment target in glioblastoma. The authors of the glioblastoma study concluded that pharmacologic targeting of circadian networks specifically disrupted cancer stem cell growth and self-renewal.

However, whether this might be generalized to many solid tumors or even other chronic diseases remains to be elucidated, said Dr. Dallmann.

In summary, he told MNT, circadian clocks have long been recognized to modulate chronic disease on many levels. The increased mechanistic understanding has the potential to improve diagnosis and existing treatments of cancer, as well as develop a new class of clock-targeting treatments.

Dr. Chung-Han Lee is a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. He is also a member of the Kidney Cancer Associations Medical Steering Committee. He talked us through recent advances in the treatment of kidney cancer.

The development and subsequent regulatory approval of combination immunotherapy for patients with metastatic kidney cancer have led to transformative change in the lives of many patients and are the hallmark of how greater scientific understanding has impacted cancer care, Dr. Lee told MNT.

Prior to 2005, treatment for metastatic kidney cancer was very limited, with most patients passing away in less than 1 year despite undergoing treatment. According to Dr. Lee, the development of antiangiogenic drugs that inhibit the growth of new blood vessels was among the first breakthroughs to improve the outcomes for patients.

However, even with antiangiogenic drugs, most patients ultimately developed resistance to treatment, and 18 months was considered a long-term response. Next came immunotherapies.

Prior to the development of antiangiogenic medications, it was known that kidney cancer could be treated by activating the immune system to better recognize the disease. However, the tools to activate the immune system were often very nonspecific. Therefore, responses to these early immunotherapies were rare, and the side effects related to treatment were not only burdensome but also could be life threatening.

With recent advances in immunotherapy, we have demonstrated that more targeted immunotherapies that activate specific immune checkpoints are not only possible but can have substantially increased activity against disease.

Two emerging treatment approaches have now become the new standard of care for kidney cancer: dual immunotherapies (such as ipilimumab/nivolumab) or combinations of antiangiogenic targeted therapies with immunotherapies (such as axitinib/pembrolizumab).

In patients treated with ipilimumab and nivolumab, over 50% remain alive at 4 years, and with some [combined antiangiogenic and immunotherapy approaches], nearly 50% of patients remain on their initial therapy at 2 years.

Despite these advances, Dr. Lee is far from complacent, telling us that there remains considerable work to be done. [] Unfortunately, in 2021, for most patients, kidney cancer remains fatal. Even for those who have outstanding responses to treatment, most still require ongoing systemic therapy.

With the rapid improvements in treatments, the development of correlative biomarkers, and the improved biologic understanding of the disease, we have only started to entertain the possibility of curative, time-limited therapy.

Building on the sacrifices of patients and caregivers and the hard work of clinicians, research staff, and scientists, a cure may, one day, be a reality for our patients, he concluded.

Our study from late 2020 has shown that the antidepressant sertraline helps to inhibit the growth of cancer cells in mice, Prof. Kim De Keersmaecker from KU LEUVEN in Belgium told MNT.

Other studies had already indicated that the commonly used antidepressant has anticancer activity, but there was no explanation for the cause of this. Weve been able to demonstrate that sertraline inhibits the production of serine and glycine, causing decreased growth of cancer cells.

Cancer cells and healthy cells are often reliant on the amino acids serine and glycine, which they extract from their environment. However, certain cancer cells produce serine and glycine within the cell. They can become addicted to this production.

This internal production of serine and glycine requires certain enzymes, and these enzymes have become targets for cancer researchers. Preventing them from functioning can starve the cancer cells.

Previous studies have identified inhibitors of serine/glycine synthesis enzymes, but none have reached the clinical trial stage. As the authors of a KU LEUVEN study note, because sertraline is a clinically used drug that can safely be used in humans, it might make a good candidate.

Prof. De Keersmaecker explained that when used with other therapeutics, the drug strongly inhibited the growth of cancer cells in the mice.

The authors of the study concluded: Collectively, this work provides a novel and cost efficient treatment option for the rapidly growing list of serine/glycine synthesis-addicted cancers.

Christy Maksoudian from the NanoHealth & Optical Imaging Group team at KE LEUVEN is excited about the promise of nanotechnology for the treatment of cancer. She told MNT that because of the unique properties that emerge at such a small scale, nanoparticles can be designed in a multitude of ways to exhibit specific behaviors in organisms.

Currently, she explained, many available nanoformulations in the clinic are composed of organic materials because of their biocompatibility and safety. In this context, organic refers to compounds that include carbon.

However, she explains that inorganic nanomaterials, which do not contain carbon, also hold promise for cancer treatment because they possess further functionalities.

For instance, some magnetic nanoparticles, such as those of superparamagnetic iron oxide, can be magnetically guided toward the tumor, while gold nanoparticles generate heat upon exposure to near-infrared light and can, therefore, be used for photothermal therapy (via tumor tissue ablation).

In short, it is possible to introduce gold nanoparticles to the bloodstream of people with cancer. From there, these nanoparticles accumulate in tumors because tumors have particularly leaky blood vessels. Once that region is exposed to near-infrared light, the gold nanoparticles heat up and, consequently, kill cancer cells.

Because of the potential of such broad range of nanomaterial designs, there are always novel cancer therapies being developed.

Christy Maksoudian

I am excited to take part in this movement with my work on copper oxide nanoparticles. Maksoudian and her colleagues use copper oxide nanoparticles doped with 6% iron.

Maksoudian told MNT that these nanoparticles exploit intrinsic metabolic differences between cancer cells and healthy cells to induce high levels of toxicity in cancer cells while only causing reversible damage in healthy tissue.

The fact that such cancer-selective properties can arise due to minor modifications of the nanoparticles at the nanoscale is truly extraordinary and reaffirms the significant role that nanomedicine can play in expanding the treatment landscape for oncology.

Cancer is complex, so approaches to its treatment must match that complexity. As the summaries above demonstrate, scientists are not short on ingenuity, and the battle against cancer continues at pace.

Read the first part of our series on cancer researchers and their exciting work here.

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Cancer research: New advances and innovations - Medical News Today

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Episode 44

In Sub-Saharan Africa, malaria is a leading cause of death for children under five and with an estimated 220 million cases worldwide every year, malaria remains a public health crisis.

For some, genetically modified mosquitoes could be a game-changing tool in the fight against malaria and other mosquito-borne diseases. But others say that genetic engineering threatens the delicate circle of life.

The World Health Organization has just released an updated version of its Guidance framework for testing of genetically modified mosquitoes. Our reporter Michael Kaloki finds out what genetically modified mosquitoes are, why guidance has been developed around this research, and what it all means for Africa.

Send us your questions from anywhere in the world text or voice message via WhatsApp to +254799042513.

Africa Science Focus, with Selly Amutabi.

This programme was funded by the European Journalism Centre, through the European Development Journalism Grants programme, with support from the Bill & Melinda Gates Foundation.

Excerpt from:
Genetically modified mosquitoes and Africa - SciDev.Net

UC San Diego scientists have modified the genome of fruit flies using CRISPR-based technologies to create eight reproductively isolated species. In the future, this technique can be adapted to other organisms including plants, insects and vertebrates to provide new biocontrol opportunities. Credit: Akbari lab, UC San Diego

Researchers create novel CRISPR-based fly species as a new method of controlling gene drive spread.

CRISPR-based technologies offer enormous potential to benefit human health and safety, from disease eradication to fortified food supplies. As one example, CRISPR-based gene drives, which are engineered to spread specific traits through targeted populations, are being developed to stop the transmission of devastating diseases such as malaria and dengue fever.

But many scientists and ethicists have raised concerns over the unchecked spread of gene drives. Once deployed in the wild, how can scientists prevent gene drives from uncontrollably spreading across populations like wildfire?

Now, scientists at the University of California San Diego and their colleagues have developed a gene drive with a built-in genetic barrier that is designed to keep the drive under control. Led by molecular geneticist Omar Akbaris lab, the researchers engineered synthetic fly species that, upon release in sufficient numbers, act as gene drives that can spread locally and be reversed if desired.

The scientists describe their SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species) development as a proof-of-concept innovation that could be portable to other species such as insect disease vectors. Spreading gene drives that limit pests that feast on valuable food crops is another example of a potential SPECIES application.

Gene drives can potentially spread beyond intended borders and be hard to control. SPECIES offers a way to control populations in a very safe and reversible manner, said Akbari, a UC San Diego Division of Biological Sciences associate professor and senior author of the paper, which is published in the journalNature Communications.

The idea behind the creation of SPECIES is reflective of the formation of new species in nature. As members of a single species separate over time, due to, for example, a new land formation, earthquake separation or other geological event, a new species eventually can evolve from the physical disconnection. If the new species eventually returns to mate with the original species, they could produce unviable offspring due to biological changes following the separation through a natural phenomenon known as reproductive isolation.

Working in the fly species Drosophila melanogaster, UC San Diego researchers and their colleagues at the California Institute of Technology, UC Berkeley and the Innovative Genomics Institute used CRISPR genetic-editing technologies to develop flies encoding SPECIES systems that are reproductively incompatible with wild versions of D. melanogaster.

Even though speciation happens consistently in nature, creating a new artificial species is actually a pretty big bioengineering challenge, said Anna Buchman, the lead author of the paper. The beauty of the SPECIES approach is that it simplifies the process, giving us a defined set of tools we need in any organism to elegantly bring about speciation.

Conceptually, when SPECIES are deployed in the wild in sufficient numbers, they can controllably drive through a population and replace all of their wild counterparts as they spread. Using malaria as an example, SPECIES mosquitoes could be developed with a genetic element that makes them incapable of transmitting malaria.

You can spread an anti-malaria SPECIES into a target population in a confinable and controllable way, said Akbari. Since SPECIES are incompatible with wild-type mosquitoes, their populations can be controlled and reversed by limiting their threshold population below 50 percent. This gives you the ability to confine and reverse its spread if desired.

As the SPECIES barrier completes its role in temporarily replacing wildtype populations, their numbers can be reduced with the reintroduction of wild type populations.

This essentially allows us to harness all of the power of gene driveslike disease elimination or crop protectionwithout the high risk of uncontrollable spread, said Akbari.

Reference: Engineered reproductively isolated species drive reversible population replacement by Anna Buchman, Isaiah Shriner, Ting Yang, Junru Liu, Igor Antoshechkin, John M. Marshall, Michael W. Perry and Omar S. Akbari, 2 June 2021, Nature Communications.DOI: 10.1038/s41467-021-23531-z

Coauthors of the paper include Anna Buchman, Isaiah Shriner (former UC San Diego undergraduate student), Ting Yang, Junru Liu (current Biological Sciences PhD student), Igor Antoshechkin, John Marshall, Michael Perry and Omar Akbari.

Funding: UC San Diego, DARPA Safe Genes Program

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Researchers Engineered a New Synthetic Fly Species Here's Why - SciTechDaily

Scientists investigate the evolution of Mimivirus, one of the worlds largest viruses, through how they replicate DNA. Credit: Indian Institute of Technology Bombay

Researchers from the Indian Institute of Technology Bombay shed light on the origins of Mimivirus and other giant viruses, helping us better understand a group of unique biological forms that shaped life on Earth. In their latest study published in Molecular Biology and Evolution, the researchers show that giant viruses may have come from a complex single-cell ancestor, keeping DNA replication machinery but shedding genes that code for other vital processes like metabolism.

2003 was a big year for virologists. The first giant virus was discovered in this year, which shook the virology scene, revising what was thought to be an established understanding of this elusive group and expanding the virus world from simple, small agents to forms that are as complex as some bacteria. Because of their link to disease and the difficulties in defining themthey are biological entities but do not fit comfortably in the existing tree of life viruses incite the curiosity of many people.

Scientists have long been interested in how viruses evolved, especially when it comes to giant viruses that can produce new viruses with very little help from the hostin contrast to most small viruses, which utilize the hosts machinery to replicate.

Even though giant viruses are not what most people would think of when it comes to viruses, they are actually very common in oceans and other water bodies. They infect single-celled aquatic organisms and have major effects on the latters population. In fact, Dr. Kiran Kondabagil, molecular virologist at the Indian Institute of Technology (IIT) Bombay, suggests, Because these single-celled organisms greatly influence the carbon turnover in the ocean, the viruses have an important role in our worlds ecology. So, it is just as important to study them and their evolution, as it is to study the disease-causing viruses.

Scientists investigate the evolution of Mimivirus, one of the worlds largest viruses, through how they replicate DNA. Researchers from the Indian Institute of Technology Bombay shed light on the origins of Mimivirus and other giant viruses, helping us better understand a group of unique biological forms that shaped life on earth. Credit: Indian Institute of Technology Bombay

In a recent study, the findings of which have been published in Molecular Biology and Evolution, Dr. Kondabagil and co-researcher Dr. Supriya Patil performed a series of analyses on major genes and proteins involved in the DNA replication machinery of Mimivirus, the first group of giant viruses to be identified. They aimed to determine which of two major suggestions regarding Mimivirus evolutionthe reduction and the virus-first hypotheses were more supported by their results. The reduction hypothesis suggests that the giant viruses emerged from unicellular organisms and shed genes over time; the virus-first hypothesis suggests that they were around before single-celled organisms and gained genes, instead.

Dr. Kondabagil and Dr. Patil created phylogenetic trees with replication proteins and found that those from Mimivirus were more closely related to eukaryotes than to bacteria or small viruses. Additionally, they used a technique called multidimensional scaling to determine how similar the Mimiviral proteins are. A greater similarity would indicate that the proteins coevolved, which means that they are linked together in a larger protein complex with coordinated function. And indeed, their findings showed greater similarity. Finally, the researchers showed that genes related to DNA replication are similar to and fall under purifying selection, which is natural selection that removes harmful gene variants, constraining the genes and preventing their sequences from varying. Such a phenomenon typically occurs when the genes are involved in essential functions (like DNA replication) in an organism.

Taken together, these results imply that Mimiviral DNA replication machinery is ancient and evolved over a long period of time. This narrows us down to the reduction hypothesis, which suggests that the DNA replication machinery already existed in a unicellular ancestor, and the giant viruses were formed after getting rid of other structures in the ancestor, leaving only replication-related parts of the genome.

Our findings are very exciting because they inform how life on earth has evolved, Dr. Kondabagil says. Because these giant viruses probably predate the diversification of the unicellular ancestor into bacteria, archaea, and eukaryotes, they should have had major influence on the subsequent evolutionary trajectory of eukaryotes, which are their hosts.

In terms of applications beyond this contribution to basic scientific knowledge, Dr. Kondabagil feels that their work could lay the groundwork for translational research into technology like genetic engineering and nanotechnology. He says, An increased understanding of the mechanisms by which viruses copy themselves and self-assemble means we could potentially modify these viruses to replicate genes we want or create nanobots based on how the viruses function. The possibilities are far-reaching!

Reference: Coevolutionary and Phylogenetic Analysis of Mimiviral Replication Machinery Suggest the Cellular Origin of Mimiviruses by Supriya Patil and Kiran Kondabagil, 11 February 2021, Molecular Biology and Evolution.DOI: 10.1093/molbev/msab003

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Scientists Use DNA To Trace the Origins of Giant Viruses - SciTechDaily

REHOVOT, Israel, June 4, 2021 /PRNewswire/ --CollPlant (NASDAQ: CLGN), a regenerative and aesthetic medicine company, announced today the uplisting of its ordinary shares to the Nasdaq Global Select Market effective at the open of market today, Friday, June 4, 2021.

CollPlant's ordinary shares now trade under the Company's current ticker symbol "CLGN" and the Company's American Depositary Shares (ADSs) have been mandatorily cancelled and exchanged for ordinary shares at a one-for-one ratio.Shareholders holding their ADSs in book-entry or through a bank, broker, or other nominee form do not need to take any action in connection with the mandatory exchange.

"We are pleased to complete this important milestone and believe that our current and future shareholders will benefit from our Nasdaq Global Marketstatus and the transition to ordinary shares," stated Yehiel Tal, CollPlant CEO.

A listing on the Nasdaq Global Marketis considered an indicator of status and success for companies that qualify for listing. Listed companies must satisfy stringent financial, liquidity and corporate governance requirements, both initially and on an ongoing basis.

About CollPlant

CollPlant is a regenerative and aesthetic medicine company focused on 3D bioprinting of tissues and organs, and medical aesthetics. The Company's products are based on its rhCollagen (recombinant human collagen) produced with CollPlant's proprietary plant based genetic engineering technology. These products address indications for the diverse fields of tissue repair, aesthetics, and organ manufacturing, and are ushering in a new era in regenerative and aesthetic medicine. CollPlant recently entered into a development and global commercialization agreement for dermal and soft tissue fillers with Allergan, an AbbVie company, the global leader in the dermal filler market.

For more information, visithttp://www.collplant.com.

Safe Harbor Statements

This press release may include forward-looking statements. Forward-looking statements may include, but are not limited to, statements relating to CollPlant's objectives plans and strategies, as well as statements, other than historical facts, that address activities, events or developments that CollPlant intends, expects, projects, believes or anticipates will or may occur in the future. These statements are often characterized by terminology such as "believes," "hopes," "may," "anticipates," "should," "intends," "plans," "will," "expects," "estimates," "projects," "positioned," "strategy" and similar expressions and are based on assumptions and assessments made in light of management's experience and perception of historical trends, current conditions, expected future developments and other factors believed to be appropriate. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Many factors could cause CollPlant's actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to, the following: the Company's history of significant losses, its ability to continue as a going concern, and its need to raise additional capital and its inability to obtain additional capital on acceptable terms, or at all; the impact of the COVID-19 pandemic; the Company's expectations regarding the timing and cost of commencing clinical trials with respect to tissues and organs which are based on its rhCollagen based BioInk and products for medical aesthetics; the Company's ability to obtain favorable pre-clinical and clinical trial results; regulatory action with respect to rhCollagen based BioInk and medical aesthetics products including but not limited to acceptance of an application for marketing authorization review and approval of such application, and, if approved, the scope of the approved indication and labeling; commercial success and market acceptance of the Company's rhCollagen based products in 3D Bioprinting and medical aesthetics; the Company's ability to establish sales and marketing capabilities or enter into agreements with third parties and its reliance on third party distributors and resellers; the Company's ability to establish and maintain strategic partnerships and other corporate collaborations; the Company's reliance on third parties to conduct some or all aspects of its product manufacturing; the scope of protection the Company is able to establish and maintain for intellectual property rights and the Company's ability to operate its business without infringing the intellectual property rights of others; the overall global economic environment; the impact of competition and new technologies; general market, political, and economic conditions in the countries in which the Company operates; projected capital expenditures and liquidity; changes in the Company's strategy; and litigation and regulatory proceedings. More detailed information about the risks and uncertainties affecting CollPlant is contained under the heading "Risk Factors" included in CollPlant's most recent annual report on Form 20-F filed with the SEC, and in other filings that CollPlant has made and may make with the SEC in the future. The forward-looking statements contained in this press release are made as of the date of this press release and reflect CollPlant's current views with respect to future events, and CollPlant does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Contact at CollPlant:Eran RotemDeputy CEO & Chief Financial OfficerTel: + 972-73-2325600Email:[emailprotected]

SOURCE CollPlant

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CollPlant Announces Effectiveness of Uplisting to the Nasdaq Global Market; Ordinary Shares Replace ADSs - PRNewswire

DetailsCategory: DNA RNA and CellsPublished on Sunday, 06 June 2021 12:38Hits: 418

8 of 11 Patients in Dose Escalation Cohorts 2 and 3 Achieved Objective Response

6 of 11 Patients Achieved Complete Response, including 2 Patients Previously Treated with Autologous CD19 CAR T-cell Therapy

Favorable FT516 Safety Profile Was Observed; No FT516-related Serious Adverse Events or FT516-related Grade 3 or Greater Adverse Events

Outpatient Treatment Regimen Was Well-tolerated; No Events of Any Grade of Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, or Graft-vs-Host Disease

SAN DIEGO, CA, USA I June 04, 2021 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim Phase 1 data from the Companys FT516 program for patients with relapsed / refractory B-cell lymphoma at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting being held virtually June 4-8, 2021. FT516 is the Companys universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The ongoing Phase 1 dose-escalation study of FT516 is currently enrolling patients in the fourth dose cohort of 900 million cells per dose.

As of the data cutoff date of March 11, 2021, four patients in the second dose cohort of 90 million cells per dose and seven patients in the third dose cohort of 300 million cells per dose were evaluable for assessment of safety and efficacy. Eight of eleven patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria (see Table 1). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.

These additional data from our Phase 1 study of FT516 administered off-the-shelf in the outpatient setting continue to reinforce its differentiated safety profile and underscore its potential clinical benefit, said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. Based on the favorable therapeutic profile of FT516 that continues to emerge and the potential to treat patients on-demand without delay, we plan to initiate multiple indication-specific, dose-expansion cohorts for patients with B-cell lymphomas to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including those used as standard-of-care in earlier-line settings.

The ongoing Phase 1 clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Safety DataNo dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). All Grade 3 or greater TEAEs were consistent with lympho-conditioning chemotherapy and underlying disease. Of note, a Grade 3 or greater TEAE of infection was reported in one patient only. There were no discontinuations due to adverse events, and no patients withdrew from the study except in the setting of disease progression. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Activity DataAs of the data cutoff date of March 11, 2021, eleven relapsed / refractory patients in the second and third dose cohorts were evaluable for assessment of safety and efficacy. Of the eleven patients, nine patients completed both FT516 treatment cycles and eight patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. Two patients showed progressive disease following the first FT516 treatment cycle and discontinued treatment. The Company previously reported that two patients treated in the first dose cohort (30 million cells per dose) showed progressive disease.

Patient Case StudyThe ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. Subsequent to the data cutoff date of March 11, 2021, the patient completed a second FT516 treatment cycle after which the response assessment continued to show complete response.

As of March 11, 2021 database entry. Data subject to source document verification.CR = Complete Response; PR = Partial Response; PD = Progressive DiseaseCAR = Chimeric antigen receptor; DH/DE = Double-hit / double expressor; DLBCL = Diffuse large B-cell lymphoma; FL = Follicular lymphoma; Gr = Grade; HGBCL = High-grade B-cell lymphoma; iNHL = Indolent non-Hodgkin lymphoma; TH = Triple-hit; Transformed iNHL = Aggressive B-cell lymphoma transformed from indolent non-Hodgkin lymphoma1 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria2 Subject did not proceed to Cycle 23 Confirmed DLBCL (transformation from Gr3A FL) subsequent to the data cutoff date of March 11, 20214 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of March 11, 2021

CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome;M = Million; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event1 Includes two subjects in the first dose cohort of 30 million cells per dose

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

SOURCE: Fate Therapeutics

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Fate Therapeutics Highlights Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma at 2021 ASCO...