Category Archives: Human Longevity

Tulsa, OK, Oct. 26, 2021 (GLOBE NEWSWIRE) -- viaNewMediaWire --AppSwarm, Corp. (OTC:SWRM), a software development company and aggregator of mobile applications, announced it has begun beta testing its own brand of consumer smartwatches for the wearable health and longevity market.

The Company is pleased to announce it has begun beta testing on its own brand of smartwatch devices that will provide health data to users, and open the door to customized add-on subscription cloud services.

Our team will begin testing functionality, and mobile SDK for data integration with third-party applications. Upon successful completion, the company will conduct an initial soft launch, with a hopeful goal of the holiday season.

SmartWatch Features

- Activity (steps, calories, distance)- Heart rate- Blood Oxygen- Sleep (total duration, deep sleep, light sleep)- Sports mode (walking, running, cycling, swimming, climbing, etc.)

The Company will utilize data generated from its wearable devices and sensors to develop cloud-based analytics that will monitor and analyze a users health data through long-term dataset development, utilizing artificial intelligence.

Distribution

Along with traditional online retail, the company will also work with its collaboration partner GTX Corp (GTXO) to resell our smartwatch devices where GTX has established channels of distribution.

The Company also plans to integrate its wearable devices with the GTX SmartSole platform to enable the collected biometric data to be sent to a central hub in the cloud without the need for a smartphone.

Chris Bailey, the CEO of AppSwarm, Corp., commented, "Our core mission is to develop technologies and applications for the betterment of mankind. Data has shown technology has had a negative effect on human health, both physical and mental, from the rise of metabolic diseases, depression, and anxiety. But we feel technology, deployed properly, can also be used to refocus human behavior back to a more positive aspect. Our focus on smart devices geared towards human health goes towards our mission to leverage technology that can potentially assist society and expand human longevity."

A more detailed roadmap and timeline of our smart device operations will be released shortly.

About APPSWARM

AppSwarm is a technology company specializing in accelerated development and publishing of mobile apps and other software platforms for gaming and business applications and seeks to acquire symmetric business opportunities. AppSwarm partners with and assists other development firms in technology development, business management, and funding needs.

For more information, visit us atwww.app-swarm.comor follow us onwww.facebook.com/AppSwarmTwitterhttps://twitter.com/AppSwarmor Instagramhttps://www.instagram.com/appswarm/

Forward-Looking Statements:

"Safe Harbor" statement under the Private Securities Litigation Reform Act of 1995: This press release may contain forward-looking statements that are subject to risk and uncertainties including, but not limited to, the impact of competitive products, product demand, market acceptance risks, fluctuations in operating results, political risk, and other risks detailed from time to time in the Company's filings with OTCMarkets.com and as required to the Securities and Exchange Commission. These risks could cause SWRM's actual results to differ materially from those expressed in any forward-looking statements made by, or on behalf of, the Company.

Investor and Media Contacts:

AppSwarm, Corp.888-886-8583info@app-swarm.com

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AppSwarm Begins Beta Testing Smart Watch Device for Health

Healthy Longevity Initiative Grant Awarded to Study the Mycobiome as a Novel Class of Probiotics to Target Inflammaging

CAMBRIDGE, Mass., Nov. 4, 2021 /PRNewswire/ -- Solarea Bio, a biotechnology company in Cambridge, Mass., and leading researchers at Harvard Medical School affiliated Hebrew SeniorLife, New England's largest nonprofit provider of senior health care and living communities, are co-investigators on a competitive research grant from the U.S. National Academy of Medicine's Healthy Longevity Initiative.

(PRNewsfoto/Solarea Bio)

Solarea Bio, along with Douglas P. Kiel, M.D., M.P.H., Director, Musculoskeletal Research Center, Hinda and Arthur Marcus Institute for Aging Research, and Shivani Sahni, Ph.D., Director, Nutrition Program, Marcus Institute, received the grant.

According to the researchers, "An aging population has led to a significant global increase in age-related diseases including cardiovascular disease, Alzheimer's, and others. At the core of this is chronic low-grade inflammation known as inflammaging, and recent evidence describes the gut microbiome as a key regulator of the inflammaging process through direct impact on immune system development and function."

However, while the impact bacteria have on the immune system and human health is well described, fungi, a major component of the gut microbiome, have been largely overlooked due to multiple factors including fungi's large, complex genomes that require deep sequencing and a hybrid assembly, lack of fungal genome databases for functional gene prediction, and underdeveloped bioinformatic tools to identify fungal metabolites important to human health.

The researchers hypothesize that the "mycobiome" (the collection of fungi that are part of the overall microbiome) could offer a large, untapped reservoir of probiotic fungi with the ability to combat inflammaging. Based on this hypothesis, the team will be working to sequence a subset of a large fungal collection and develop bioinformatic tools to identify fungi with probiotic potential. Lead candidate fungi will be tested using in vitro cell culture systems to identify fungi with anti-inflammatory properties that may then be further tested clinically.

Story continues

About the Healthy Longevity InitiativeThe Healthy Longevity Initiative is designed to kick start innovation to support healthy longevity through a series of monetary awards and prizes. In the tradition of international races to fly across the Atlantic or walk on the moon, the initiative will rally the world's greatest minds to achieve what may at first seem an impossible goal.

About the Hinda and Arthur Marcus Institute for Aging ResearchScientists at the Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making.

About Hebrew SeniorLifeHebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Hebrew SeniorLife cares for more than 3,000 seniors a day across six campuses throughout Greater Boston. Our locations include: Hebrew Rehabilitation Center-Boston and Hebrew Rehabilitation Center-NewBridge in Dedham; NewBridge on the Charles, Dedham; Orchard Cove, Canton; Simon C. Fireman Community, Randolph; Center Communities of Brookline, Brookline; and Jack Satter House, Revere. Founded in 1903, Hebrew SeniorLife also conducts influential research into aging at the Hinda and Arthur Marcus Institute for Aging Research, which has a portfolio of more than $63 million, making it the largest gerontological research facility in the U.S. in a clinical setting. It also trains more than 1,000 geriatric care providers each year. For more information about Hebrew SeniorLife, visit https://www.hebrewseniorlife.org or follow us on our blog, Facebook, Instagram, Twitter, and LinkedIn.

About Solarea BioSolarea Bio is a biotechnology company based in Cambridge, Mass. developing new microbiome-based solutions to some of the world's largest health problems. Solarea was founded in 2017 by a group of scientists and entrepreneurs eager to radically alter our understanding of the human microbiome and utilize its power to improve human health. Solarea's breakthrough came from the combined efforts of the company's co-founders who established a link between the discovery of an untapped source of microorganisms with probiotic potential in healthy foods, and their applications in inflammatory processes including the gut-musculoskeletal axis.

Media Contacts:Margaret BonillaHebrew SeniorLife617-363-8367margaretbonilla@hsl.harvard.edu

Rachel Raymond Solarea Biorraymond@solareabio.com

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Solarea Bio Teams up with Hebrew SeniorLife Investigators on a Newly Awarded U.S. National Academy of Medicine Catalyst Grant - Yahoo Finance

If ones thirties were a decrepit old age, ancient writers and politicians dont seem to have got the message. In the early 7th Century BC, the Greek poet Hesiod wrote that a man should marry when you are not much less than 30, and not much more. Meanwhile, ancient Romes cursus honorum the sequence of political offices that an ambitious young man would undertake didnt even allow a young man to stand for his first office, that of quaestor, until the age of 30 (under Emperor Augustus, this was later lowered to 25; Augustus himself died at 75). To be consul, you had to be 43 eight years older than the USs minimum age limit of 35 to hold a presidency.

In the 1st Century, Pliny devoted an entire chapter of The Natural History to people who lived longest. Among them he lists the consul M Valerius Corvinos (100 years), Ciceros wife Terentia (103), a woman named Clodia (115 and who had 15 children along the way), and the actress Lucceia who performed on stage at 100 years old.

Then there are tombstone inscriptions and grave epigrams, such as this one for a woman who died in Alexandria in the 3rd Century BC. She was 80 years old, but able to weave a delicate weft with the shrill shuttle, the epigram reads admiringly.

Not, however, that ageing was any easier then than it is now. Nature has, in reality, bestowed no greater blessing on man than the shortness of life, Pliny remarks. The senses become dull, the limbs torpid, the sight, the hearing, the legs, the teeth, and the organs of digestion, all of them die before us He can think of only one person, a musician who lived to 105, who had a pleasantly healthy old age. (Pliny himself reached barely half that; hes thought to have died from volcanic gases during the eruption of Mt Vesuvius, aged 56).

In the ancient world, at least, it seems people certainly were able to live just as long as we do today. But just how common was it?

Age of empires

Back in 1994 a study looked at every man entered into the Oxford Classical Dictionary who lived in ancient Greece or Rome. Their ages of death were compared to men listed in the more recent Chambers Biographical Dictionary.

Of 397 ancients in total, 99 died violently by murder, suicide or in battle. Of the remaining 298, those born before 100BC lived to a median age of 72 years. Those born after 100BC lived to a median age of 66. (The authors speculate that the prevalence of dangerous lead plumbing may have led to this apparent shortening of life).

The median of those who died between 1850 and 1949? Seventy-one years old just one year less than their pre-100BC cohort.

Of course, there were some obvious problems with this sample. One is that it was men-only. Another is that all of the men were illustrious enough to be remembered. All we can really take away from this is that privileged, accomplished men have, on average, lived to about the same age throughout history as long as they werent killed first, that is.

Still, says Scheidel, thats not to be dismissed. It implies there must have been non-famous people, who were much more numerous, who lived even longer, he says.

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Do we really live longer than our ancestors? - BBC Future

Moral Or Ethical Problems Associated With Eating Meat

The third reason, ethical or moral concerns, is very personal and varies considerably among each person who chooses to adopt a vegetarian or vegan diet for such reasons. A secondary question, however, also presents itself. With so many people moving towards vegetarianism or veganism, and evidence showing the health benefits to be found in reducing meat consumption, why is the demand for meat still soaring? Why arent more people moving into a vegetarian or vegan diet? There may be a wide variety of answers to this question but lets address just one for now.

Humans have been eating meat for many thousands of years, and it is essentially part of our culture. Put simply: we like it. Most people around the world enjoy the flavors, smells, and texture of meat. Some visionaries have, however, made a lot of progress in bridging these two contrary positions. Plant-based meat is now significantly tastier. Its also a lot more like real meat. The choices now available are also wider than ever before. Start-ups and major companies alike are now producing vegan steaks, vegan sausages, vegan kabobs, and a multitude of other plant-based meat options.

Some may ask if we really need to mimic the taste of meat? Shouldnt we just try to move towards a vegetarian diet? Different people will come to different answers to this question, but as noted, giving up meat is not quite as easy as it sounds.

The people who create vegan meat understand this problem and are doing their best to produce solutions that can satisfy the cravings many people feel for meat.

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Changing Hearts And Minds With Vegan Meat - Longevity LIVE - Longevity LIVE

Palm Beach, Florida--(Newsfile Corp. - November 3, 2021) - In an effort that will expand the Company's technology leadership, JZZ Technologies, Inc. (OTC Pink: JZZI) has added Michael Wiley in a key position that will advise the board and leadership on acquisitions and the build-out of future technology capabilities.

In his more than 25 years of working in the Technology Industry at tech startups Cisco Systems, JPMorgan, Google, and F5 Networks, Inc. as Application CTO, Mr. Wiley has led many engineering teams, software, and product solutions at a massive scale. His extensive knowledge of cloud, mobile, and advanced applications will be a great addition to JZZ Technologies, Inc. He has also implemented products and engineering strategies for key industries ranging from non-profits, retail, service industries, emerging markets, and the financial sector. His guidance will be instrumental in leading and managing JZZ Technologies' corporate strategies and the ability to employ key technologies for its customers.

"We have been making tremendous progress as a company, and our initiatives have reached a point where we require a skilled and capable professional like Michael Wiley to advise on our technology strategies, capabilities and acquisitions," says Charles Cardona, CEO of JZZ Technologies, Inc.

"Mr. Wiley has an impressive background in building software and engineering organizations at hyper-scale, launching products, and building within many challenging market sectors. He brings a diverse set of talents to the table, along with a fantastic work ethic. His experience will be critical as we expand our digital properties and other ventures, particularly in advancing our technologies, acquisitions and further our market impact. We are fortunate to have Michael Wiley joining JZZ Technologies Inc. to help guide our team," Cardona added.

About JZZ Technologies, Inc.

JZZ Technologies, Inc. is a diversified technology company rolling up projects and partnerships in two distinct business sectors that operate cohesively; its digital media business includes online media and apps (activelifestylemedia.com), content creation, digital marketing, streaming video content, publishing, and free over-the-air television (EyeOnTV) targeted at active adults 55+. The Company's other business is focused on strategic biotechnology and bioscience acquisitions related to Human Life Extension and Human Longevity that can be immediately leveraged to support improved quality of life for aging populations.

DISCLAIMER and FORWARD-LOOKING STATEMENTS

Certain statements contained herein are "forward-looking" statements (as such term is defined in the Private Securities Litigation Reform Act of 1995). Because such statements include risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities and Exchange Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended, and such Forward-Looking Statements are intended to be covered by the safe harbors created thereby. Investors are cautioned that all forward-looking statements involve risks and uncertainties. All statements other than statements of historical fact in this announcement are forward-looking statements, including but not limited to the viability of the company's business plans, the effect of acquisitions on our profitability, the effectiveness, profitability, and the marketability of the Company's products; the Company's ability to protect its proprietary information; general economic and business conditions; the volatility of the company's operating results and financial condition; and other risks detailed in the Company's filings with the Securities and Exchange Commission. These forward-looking statements involve known and unknown risks and uncertainties and are based on current expectations, assumptions, estimates, and projections about the company and the industry. The Company undertakes no obligation to update forward-looking statements to reflect subsequent occurring events or circumstances or to changes in its expectations, except as may be required by law. Although the company believes that the expectations expressed in these forward-looking statements are reasonable, management cannot assure the public that their expectations will turn out to be correct. Investors are cautioned that actual results may differ materially from the anticipated results.

Contact: JZZ Technologies, Inc. Charles Cardona, CEO Email: ccardona@jzztechnologies.com Website: https://www.jzztechnologies.com/

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/101822

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JZZ Technologies, Inc. Expands Technology Leadership with Addition of Michael Wiley as Board Advisor - Stockhouse

DALLAS (PRWEB) November 05, 2021

Texas-based investor John A. Kuelbs announces his commitment to transformative health initiatives with his investment in Elevian, an emerging biotech company developing medicines that restore youthful regenerative capacity, with the potential to treat and prevent multiple age-related diseases.

Over the past century in America, the average life expectancy has increased from 50 years to 80 years. Given the ever-increasing progress of scientific understanding, I think its quite possible to achieve a lifespan of 100 reasonably healthy years, said Kuelbs. Elevian is one of the top companies working to enhance longevity, with impressive preclinical data demonstrating the ability to therapeutically repair damaged tissues and organs.

The Series A funding round will enable Elevian to submit an investigational new drug application, scale manufacturing and complete Phase 1 clinical trials for its lead indication of stroke recovery the first of many potential applications for its breakthrough drug candidate.We are pleased to have the Kuelbs family as investors in Elevian and John as a business advisor, said Dr. Mark Allen, Co-Founder and CEO of Elevian. His insight and experience building valuable companies across numerous industries provide a valuable perspective to the company.

About ElevianElevian is an emerging biotech company developing medicines that restore youthful regenerative capacity, with the potential to treat and prevent multiple age-related diseases. Elevian's scientific founders, working at the Harvard Department of Stem Cell and Regenerative Biology, discovered that treatment with the circulating factor GDF11 can regenerate the heart, brain, muscle and other tissues. Elevian has acquired exclusive, worldwide rights to Harvard's patent portfolio concerning GDF11. The company is developing new medicines that target the GDF11 pathway. Elevian's lead drug candidate (recombinant human GDF11) has demonstrated efficacy in preclinical models of stroke, obesity, Type 2 diabetes, heart failure, Alzheimer's disease, and many other age-related diseases. The company has also established additional programs focused on the discovery and development of novel proteins, antibodies and small molecule drugs that target the GDF11 pathway. For more information, please visit http://www.elevian.com

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Kuelbs Family Office Invests in Biotech Company Elevian, Supporting $40 Million Funding Round - PR Web

In 2009, the U.S. Special Operations Command announced that Humans are more important than hardware. But with wearables revolutionizing sports medicine and athletics, the distinction between humans and hardware is less relevant than ever. This means that investing in wearable technology for special operations forces is now the best way to put humans first.

What might this look like? With a small population of elite warfighters in high-stress environments, Special Operations Command can lead the force in determining which wearable devices are worth the investment. The Preservation of the Force and Family program, which is already in place to improve the holistic health of special operations forces, can spearhead efforts to distribute, monitor, test, and best utilize wearables for the entire military.

A Wearable Revolution

In the last two decades, sports medicine and sports science have advanced dramatically. Athletes are now bigger, faster, and stronger due, in part, to advancements in technologies that allow them to train smarter. A critical facet of this revolution is wearable technology that offers athletes immediate and continuous feedback on an increasing number of health and performance metrics. The wearable trend started with simple Global Positioning System-enabled devices measuring steps taken in a day and heart-rate monitors allowing users to train in specific heart-rate zones. However, wearable technology is now quickly outpacing older, more expensive, and more invasive technologies. New Apple Watches, for example, allow users to bypass hospital visits by serving as both an electrocardiogram to monitor heart health and a pulse oximeter to measure blood oxygen levels in 10 seconds. Wearables rapid development is providing valuable new tools for physical therapists and healthcare professionals and eliciting optimism about the future of individualized self-care.

This revolution hasnt gone unnoticed by the Department of Defense, which is testing wearables across different military branches. The U.S. Air Force recently began using the Oura Ring, a technology worn on your finger, to more accurately determine pilots flight readiness in the morning based on their overall sleep score. Previously, pilots flight readiness was determined by hours in bed rather than the quality of sleep. However, Oura Rings offer the ability to both measure sleep quality and potentially improve sleep, making pilots fitter to fly. Additionally, the U.S. Navy regularly tests various wearable devices at the Naval Postgraduate School Human and Systems Integration laboratory to study and improve crew rest, while the U.S. Army tests wearables to study soldiers resiliency in harsh winter conditions. As wearable technology continues to progress, so do the applications and opportunities to improve service members sleep, fitness, and overall health.

Wearables Potential in Special Operations

In 2012, Special Operations Command adopted the Preservation of the Force and Family strategy. The goal was to optimize and sustain mission readiness, longevity, and performance, thereby maximizing the estimated $1.5 million investment that the military makes in each member of special operations. The strategy seeks to provide precise preventative interventions and emphasisizes holistic health across five domains: physical, cognitive, psychological, social and family, and spiritual.

Wearable technology is already improving individual physical fitness and should be a critical component in enhancing operator health across every all of these domains. Wearables currently track a host of physical and biological metrics and use algorithms to generate useful approximations of additional metrics, including sleep quality, readiness, and stress. Many wearable interfaces offer coaching to nudge users towards healthier behaviors. Leading wearables, including the Oura Ring, Apple Watch, and Whoop Strap, offer nuanced sleep and activity coaching based on users unique metrics and trends. Put simply, wearables can tell you when you are overworked and need a break.

In an organization like Special Operations Command, which demands long hours under highly stressful conditions, having a tool that provides an objective measurement of readiness is uniquely valuable. Operators are specially selected and trained for resilience to adverse physical and mental conditions. Constant adaptation to a changing environment, however, comes at a cost. But this advantageous adaptation can produce allostatic load, leading to chronic physical maladies including pain, fatigue, and compromised immunity. Reduction of allostatic load first requires identification of increased stress. Enter wearables. Wearables can provide feedback on a host of biological metrics correlated with stress, including heart-rate variability, resting heart rate, and sleep quality. This makes it possible to identify chronic physiological stress, implement nuanced interventions, and prevent the difficulties associated with allostatic overload.

Wearables can also bring benefits in the cognitive and psychological domains. The Oura Ring encourages users to monitor body signals through practices such as guided mindfulness and breathing protocols. As shown by ongoing studies at Texas A&M, mindfulness meditations and associated breathing exercises can reduce stress and improve mental health. This can be particularly useful to special operations forces in reducing combat mental illness. Paired with blast gauge data or baseline cognitive tests such as the Automated Neuropsychological Assessment Metrics, wearables may also allow the early identification and treatment of traumatic brain injury.

Mitigating Concerns

In a profession where chronic stress is so abundant that it produced the term operator syndrome, why are wearable technologies not already commonplace? For one thing, there isnt a one-size-fits-all wearable. While one wearable specializes in sleep, for example, it may not be as effective at measuring physical activity. Concerns over operational security also dampen wearable enthusiasm in the Defence Department. And for good reasons in 2018, the fitness and location tracking application Strava infamously illuminated the location of multiple overseas military bases. Similarly, privacy risks regarding collected data can cause hesitation in an increasingly connected and data-driven world. Data security and patient confidentiality are paramount concerns with aggregated health information collected from wearables, and have legal implications under the Health Insurance Portability and Accountability Act. While data is routinely stripped of identifiers, including names and addresses, it can become re-identifiable when correlated with other datasets.

Special Operations Command has an important role to play in helping to address these security and privacy concerns. Letting the Preservation of the Force and Family program lead the development of wearables can help by removing military commanders from the loop, preventing mandatory use and giving participants the power of consent. Personnel associated with this program are also trained and certified to handle protected health information, reducing the risk of a Health Insurance Portability and Accountability Act violation and relieving military commanders of such a burden. Assigning random user identifications can help to avoid the disclosure of personal data. Preservation of the Force and Family personnel can further prevent the re-identification of anonymous users by isolating the wearables data, thereby preventing their merging with larger military data sets.

While there are simple ways to mitigate the known concerns over wearables, there will always be risks, especially with the early adoption of technology. These risks should be explored, preferably in a small and competent population, to best identify and understand wearables capabilities and limitations. Implementation and open dialogue will enable the force to exploit wearables significant potential to improve holistic health.

Wearables Are Coming!

In any technological revolution, there will be resistance to adopting new technology, especially in large organizations like Special Operations Command. Nevertheless, wearable technology has taken the world by storm. Large corporations have adopted wearables into healthcare policies, and wearable tech is an $81.5 billion industry. With a smaller population that is often presented with high chronic stress, Special Operations Command has the opportunity to lead the U.S. military in the use of wearable technology. By leveraging the recent revolution in wearables, programs such as Preservation of the Force and Family can bring humans and hardware together in the safest and smartest way possible.

Maj. Kevin Butler and Maj. Frank Foss are Army Special Forces officers currently pursuing a masters in Defense Analysis at the Naval Postgraduate School. Between them, they have over a dozen combat and operational deployments to the Central Command and Southern Command.

Disclaimer: The views expressed in this article are the views of the authors alone. They do not reflect the official position of the Naval Postgraduate School, the U.S. Army, the Department of Defense, or any other entity within the U.S. government and the authors are not authorized to provide any official position of these entities.

Image: U.S. Army (Photo by Sgt. Apolonia Gaspar)

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Humans and Hardware: How Special Operations Can Pioneer Wearable Technology - War on the Rocks

CAR T-cell therapy and bispecific antibodies for T-cell redirection are 2 recent immune strategies developed in the treatment of multiple melanoma.

Multiple Myeloma is a clonal plasma cell neoplasm characterized by bone lesions, renal impairment, cytopenias, and immunodeficiency. Despite significant therapeutic advancements in the past 2 decades that have resulted in improved survival, myeloma remains an incurable disease. The immune environment in which the cancer cells thrive is known to be a key player in the evolution of monoclonal gammopathies from premalignant stages to advanced malignancy. Further, immune dysregulationmarked by T-cell exhaustion, tolerance induction by tumor microenvironment, and tumor escape from immune surveillanceis important in the pathogenesis. Therefore, various immune strategies have been developed, including immune-enhancing drugs such as immunomodulatory drugs, checkpoint inhibitors, monoclonal antibodies, and, more recently, chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for T-cell redirection.

CAR T cells are T lymphocytes genetically modified by viral vectors or nonviral technology such as DNA transposons to express a synthetic receptor to target a specific antigen. The single chain variable fragment (ScFV) on the ectodomain of the CAR recognizes tumor-associated antigens on the surface of tumor cells, binds to them, and initiates a cascade of cytotoxic signaling, that leads to tumor lysis.

The ectodomain is linked to the intracellular domains by a hinge/transmembrane region, commonly derived from CD8 or IgG4. The intracellular portion is the signaling domain. In the first generation of CARs, this included only the CD3 signaling

domain, which lacked a proliferation profile. The second- and third-generation CARs now include 1 (second generation) or 2 (third generation) costimulatory domains that are typically 4-1BB, CD28, and/or OX-40 to promote efficient T-cell signaling and persistence. Fourth-generation CARs (TRUCKs), which further affect the tumor microenvironment to induce cytokine production after the CAR recognizes the target antigens, and fifth-generation CARs are being developed to further improve CAR efficiency and longevity.

On the other hand, bispecific antibodies use patients unengineered T cells. The off-the-shelf antibody is designed so that 1 end binds to a multiple myeloma cell and the other end binds to a killer T cell. The first bispecific antibody for multiple myeloma was developed with an ScFV that attached to the tumor antigen and another that attached to CD3 of the T cell receptor complex of the T cell with a linker. The halflife was short and continuous infusion was required. Since then, bispecific antibodies are manufactured with an Fc segment that increases the half-life so that the agent can be administered weekly or less frequently; this is the treatment of choice in ongoing clinical trials. New agents in development include trispecific antibodies that may have a costimulatory protein or target dual myeloma antigens or antibodies that engage natural killer cells.

There are several tumor antigens being investigated as suitable targets for CAR T-cell and T-cell redirected therapies, such as CD38, CD138, SLAMF7, CD19, and more. However, the most widely studied target for both CAR T-cell therapies and for bispecific antibody therapies is B-cell maturation antigen (BCMA).

BCMA is a cell surface receptor in the tumor necrosis factor receptor superfamily member 17 (TNFRSF17). It is deemed an ideal antigenic target because it is expressed specifically on normal and malignant plasma cells but not on hematopoietic stem cells, and has higher expression on myeloma cells than normal plasma cells. It plays a key role in B-cell maturation and differentiation and promotes myeloma cell growth by binding to its ligands BAFF and APRIL. Expression of BCMA increases with progression from MGUS to advanced myeloma.

Based on encouraging results from the first major global multicenter phase 1 anti- BCMA CAR T study (NCT02658929) conducted in relapsed or refractory multiple myeloma1, investigators initiated the pivotal phase 2 KarMMa trial (NCT03361748).2 The results of this trial were updated at the 18th International Myeloma Workshop (IMW) held in Vienna, Austria, in September.3

Idecabtagene vicleucel (ide-cel; Abecma), formally bb2121, is an anti-BCMA second-generation CAR construct with a 41BB costimulatory domain. Among 128 patients enrolled in the KarMMa study, 84% were triple-class refractory. At a median follow-up of 24.8 months, the overall response rate (ORR) was 73%, with complete response (CR) or stringent CR (sCR) reported in 33% of responders. Minimal residual disease (MRD) was negative in 79% of complete responders. Further, responses were attained at a median of 1 month (range, 0.5-8.8) and the median duration of response (DOR) was 10.9 months.

The median progression-free survival (PFS) was 8.6 months and median overall survival (OS) was 24.8 months. DOR and PFS were improved in the higher-dose ranges and in complete responders. Similar degrees of responses were observed in all subgroups, including Revised International Staging System for multiple myeloma III criteria, extramedullary disease, and high tumor burden. In terms of adverse effects (AEs), cytopenias were observed in 97% of patients. Grade 3/4 neutropenia was seen in 89% of patients, grade 3/4 thrombocytopenia was seen in 52%, and grade 3/4 infections in 23%. Cytokine release syndrome (CRS) was seen in 84% of patients: 78% at grade 1/2, 6% at grade 3 or higher. CRS occurred at a median onset of 2 days and median duration was 5 days. Neurotoxicity was reported in 18% of patients, 4% of whom reported the AE as grade 3 or higher. Results of the study led to FDA approval of the first, commercially approved CAR T-cell product in March.

CARTITUDE-1 was a phase 1b/2 study (NCT03548207)4 that used a different CAR T product, ciltacabtagene autolecleucel (cilta-cel). Updated findings were presented from Usmani et al5 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at IMW from Jagannath et al.6

Cilta-cel is a lentiviral vector-based anti-BCMA construct with a 41BB costimulatory domain. The BCMA-catching domain targets 2 different epitopes simultaneously, increasing the binding affinity, and is the same CAR construct as in the Chinese trial LEGEND-2 (NCT03090659).

In CARTITUDE-1, 97 patients with a median of 6 prior lines of therapy were enrolled. At baseline, 88% were triple-class refractory and 99% were refractory to their last line of therapy. At a median follow-up of 18 months, the ORR was 98% for all patients and included an sCR rate of 80%. Responses were attained at a median of 1 month and deepened over time. The median DOR was 21.8 months overall (95% CI, 21.8-not estimable) and was not reached in patients with sCR. MRD negativity was achieved in 92.0% of evaluable patients.

The 18-month PFS rate was 66% (95% CI, 54.9%-75.0%) and the 18-month OS rate was 80.9% (95% CI, 71.4%-87.6%). These results far surpass outcomes with other nonT-cell mediated novel agent therapies in triple-class refractory patients.

In terms of safety, cytopenias were universal and 92 of 97 patients experienced any-grade CRS; 95% were grade 1/2 and had a median time of onset of 7 days and duration of 4 days. All-grade neurotoxicity was reported for 21% of patients, 10% of whom had neurotoxicity of grade 3 or higher. Although most neurotoxic events occurred in the setting of CRS, 12 patients had late neurotoxicity, 6 of whom resolved, 1 had ongoing neurotoxicity, and 1 died because of neurotoxicity. There were 21 deaths on study: 2 occurred in fewer than 100 days, 10 deaths were because of disease progression, and 6 were because of treatmentrelated AEs. Late recovery (greater than 1 month) of grade 3/4 cytopenias from first onset was seen in 10% of patients with neutropenia and 26% of those with thrombocytopenia.

At the American Society of Hematology (ASH) Annual Meeting 2020, Shah et al7 presented an analysis that compared efficacy outcomes seen in the KarMMa trial with those reported from the MAMMOTH study,8 which was a retrospective observational study of conventional care regimens in patients with triple-class refractory multiple myeloma.

The MAMMOTH study, which has been used in other comparative studies, has been a benchmark for investigators to compare therapeutic maneuvers in patients with triple-class exposed relapsed or refractory multiple myeloma who have received various standard-of-care therapies. The analysis applied matching-adjusted indirect comparisons to assess the efficacy of ide-cel and conventional care and showed that, in a matched population, ide-cel treatment was associated with a significantly higher ORR, PFS, and OS than conventional care.

Cilta-cel was similarly compared with conventional treatment in the MAMMOTH study and was presented by Costa et al at ASCO 2021.9 The MAMMOTH data set was used to identify patients with multiple myeloma refractory to anti- CD38 monoclonal antibodies who would meet eligibility for CARTITUDE-1 and who received conventional therapy. The intention-to-treat population (ITT) in CARTITUDE-1 was defined as patients who underwent apheresis, and a modified ITT population was defined as subset of patients who received cilta-cel at the recommended phase 2 dose (RP2D).

ORR, PFS, and OS for both the ITT population and modified ITT population in CARTITUDE-1 vs matching MAMMOTH cohorts were found to be superior. Specifically, the ORR in the ITT cohort was higher in CARTITUDE-1 compared with the MAMMOTH counterpart (84% vs 28%). Patients in the CARTITUDE-1 ITT cohort vs MAMMOTH cohort had improved PFS and OS rates at 12 months, 73% vs 12% and 83% vs 39%, respectively. Comparing the modified ITT cohorts, patients in CARTITUDE-1 had superior ORR (96% vs 30%), 12-month PFS rate (79% vs 15%) and 12-month OS rate (88% vs 41%).

Therefore, in patients with relapsed or refractory multiple myeloma beyond therapy with immunomodulatory drugs, proteasome inhibitor, and anti-CD38 monoclonal antibody, treatment with ide-cel or cilta-cel is associated with higher response rate and superior PFS and OS when compared with conventional treatment.

Other CAR T trials were reported at ASH 2020 and are being studied in various phase 1/2 trials. Research is directed at improving the efficacy and persistence of CAR products, which vary by source of product (autologous vs allogeneic CAR T cells), choice of vector (lentiviral, retroviral, or nonviral DNA transposon technology), use of humanized ScFv to prevent immunogenicity, CD4/CD8 ratio controlled to enrich for central memory phenotype to improve longevity of CAR T cells, dual target constructs to prevent relapses because of antigen escape, CARs against non-BCMA targets to treat BCMA negative relapses, and more.

Bispecific antibodies are in earlier stages of development than CAR T. The majority of anti bodies target BCMA, although there are some targeting antigens other than BCMA that have great potential in patients who have relapsed post BCMA-targeted therapies with BCMAnegative plasma cells.

Teclistamab is an anti-BCMA/anti-CD3 bispecific antibody with intravenous and subcutaneous formulations. Results of the MajesTEC-1 study (NCT03145181) were published in Lancet.10,11 Investigators treated 157 patients with a median of 6 prior lines of therapy, of whom 82% were triple-class refractory, 90% were refractory to their last regimen, and 85% were previously transplanted were enrolled to a dose escalation/ expansion study. A total of 40 patients received the RP2D of 1500 g/kg. At RP2D, the median time to response was 1 month and median time to CR was 3 months.

At a median follow-up of 7.2 months, median DOR was not reached (7.2-not reached). The ORR was 65% in the RP2D group, 58% had a very good partial response (VGPR) or better, and 40% had a CR or better. Importantly, the majority of patients in CR were MRD negative at 10-6. Among responders, 85% were alive and progression free at follow-up. The most common AEs of any grade were CRS, all grade 1 or 2 (70%), and neutropenia (65%). Grade 3 or 4 AEs occurred in 80% of patients, with the most common being neutropenia (40%), anemia (28%), and thrombocytopenia (20%). Infections occurred in 45% of patients and were grade 3 or higher in 23%.

Talquetamab is an anti-GPRC5D/CD3 first-in-class duo antibody. Results from the phase 1 MonumenTAL-1 trial (NCT04634552) were presented by Chari et al at ASH 202012 and updated at IMW by van de Donk et al.13

GPRC is highly expressed in poor-risk myeloma, and in hair follicles. In the MonumenTAL-1 trial, 174 patients with a median of 6 prior lines of therapy were enrolled, 102 to the intravenous arm and 72 to the subcutaneous formulation arm, in dose escalation and expansion cohorts. At baseline 71% of patients were triple-class refractory and 86% were refractory to last line of therapy; 21% of patients had received prior BCMA-targeted therapies.

The ORR was 70% at the RP2D, and 50% of responders had a VGPR or better, with a median time to first confirmed response of 1 month. Responses were durable and deepened over time, with 81% of responders continuing on treatment after a median follow-up of 6.3 months. CRS was reported in 79% of patients; 4% had CRS of grade 3/4. Median time to onset of CRS was a day after subcutaneous dose, and the duration was 2 days. Neurotoxicity was reported in 7% of patients (grade 1/2) and was mostly in the context of CRS. Grade 1/2 skin-related AEs were seen in 75% of patients and nail-related AEs in 18%. Dysgeusia was reported in 57% of patients. A phase 2 expansion study (MonumenTAL-2) is recruiting. Patients will receive talquetamab at the RP2D.

Various other bispecific antibodies are in clinical trials, including Regeneron 5458, another anti-BCMA/anti-CD3 bispecific antibody with very encouraging results reported at ASH last year.14 The ORR was 63% and responses were achieved by 1 month. The median DOR was 6 months, and among responders with more than 6 months of follow-up, 83% had ongoing responses for up to 13 months and 74% of responders remained on treatment. TNB-383B is a fully human triple-chain BCMA CD3 bispecific antibody with a unique anti-CD3 moiety for target lysis with minimal cytokine release and 2 anti-BCMA moieties. It is administered intravenously every 3 weeks without step-up dosing. Data for 58 patients from the ongoing first-in-human study were presented at ASH 2020.15 Safety data were comparable with results of other studies.

Cevostamab is another nonBCMA bispecific antibody. The target antigen is FcRH5, which is found on nave and memory B cells and plasma cells. The anti-FcRH5/anti-CD3 is administered intravenously every 3 weeks, and data were presented at ASH 2020 last year as well.16 Finally, CC-93269, a bispecific antibody with 1 CD3 and 2 BCMA binding sites, shows encouraging early data as well.

Future directions for bispecific antibodies include understanding resistance mechanisms, studying them in combination with various agents, and understanding sequencing strategies.

Because myeloma is marked by clonal heterogeneity, combinations of drugs with different mechanisms of action and nonoverlapping toxicities are frequently used with success. With the arrival of this new era of powerful immunotherapeutic tools such as CAR T and T-cell redirective agents, a sound understanding of their optimal use is key to maximizing their potential.

Read more from the original source:
Therapeutic Frontiers for Relapsed/Refractory Multiple Myeloma Expand With CAR T and Bispecific Antibodies - OncLive

If you ever thought that living over a 100 years could only be possible only for future generations, you might be mistaken. Technology and AI are advancing rapidly, and with the help of blockchain, longevity achievements might be not far ahead.

The Longevity Science Foundation, based in Switzerland, launched a $1 billion fund over the span of ten years for research and projects to advance human longevity and extend lifespan to 120+ years.

The non-profit organization aims to make longevity medicine available for everyone and will focus on four main research areas: therapeutics, predictive diagnostics, personalised medicine, and artificial intelligence. The foundation plans to fund the development of medical technology, which broadly includes blockchain.

Blockchain in the Medical Industry

Healthcare data is immense and creates challenges in centralization and security. On average, a hospital produces 760 terabytes of data every year. However, 80% of the data lacks structure and is inaccessible to researchers, according to an article by Garri Zmudze from Longevity Science Foundation.

The need for security and reoccurring consent of the data usage prevents progress for medical research. With the help of blockchain and AI, patient consent can be easily obtained, data can be unlocked for analysis, and its usage can be transparent.

Without blockchain, artificial intelligence lacks the ethically sourced and protected biomedical data it needs to find new solutions. Without artificial intelligence, the vast amounts of data protected by blockchain remain secure but unusable for research,the article says.

Blockchain Technology and Longevity Research

VitaDAO is a decentralized collective that funds longevity research. The web3-based organization aspires to create a world where longevity therapeutics are collectively funded, owned and governed by the population that will benefit from them.

VitaDAOs ecosystem has an open structureeveryone who owns VITA tokens can access it. To get the tokens, you need to contribute work, funds, or other resources to VitaDAO. In addition, its collective membership, rather than a CEO or a handful of grant reviewers, will decide by vote how to deploy its funding, manage its IP, and share/publish its data.

The organization already held a token auction on a crypto platform to receive funding for longevity researchers and raised $5.1 million (400% more than expected).

How Can Blockchain Help to Advance Longevity?

According to biochemist and researcher Eleanor Sheekey, there are two main ways in which blockchain can help to advance longevity. The first is through the funding of longevity projects such as through the recently launched VitaDAO. This not only raises significant funding for research projects but also aids in the commercialisation of drugs if they are successful.

The second way is by exploiting some of the features of blockchain technology such as security and storage of data, which is most relevant to the application of personalised or precision medicine whereby patient information such as genetics, blood profile data, microbiome assessments, epigenetic methylation, and sleep data could be transacted and analysed without risk of the patient data getting into the wrong hands and being exploited.

I think it is hard to tell for now what the potential of blockchain in medical research might be, but I don't foresee a future whereby blockchain technology is not a part of medical research,Sheekey told DailyCoin during an email interview.

On The Flipside

Why You Should Care?

Funding longevity projects through blockchain technology might be one of the best ways to be part of the research process. Blockchain adds many benefits to the medical industry, but poses some technical challenges.

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$1 Billion Science Fund to Use Blockchain Projects to Extend Human Lifespan By DailyCoin - Investing.com

In the early 1990s, Tom Perls met two people who would change his life. Perls, then a gerontology fellow at Harvard Medical School, was visiting Bostons Hebrew Rehabilitation Center for Ageing and needed to see a couple of patients who just happened to be over 100. But he couldnt find them in their rooms. He eventually tracked down one patient, a 103-year-old woman. She was busy playing Chopin and Mozart on the piano. Perls other patient, a 101-year-old former tailor, was discovered in the occupational health room mending his housemates clothes.

They totally surprised me and thats when the epiphany happened, says Perls, who is now based at Boston University. These folks seemed to be ageing incredibly slowly compared to other people. He wanted to figure out their longevity secrets and vowed to find as many other centenarians as he could. The project became the New England Centenarian Study, the worlds largest study of exceptionally old people.

Centenarians are less rare than they used to be. In the UK, there were 15,120 centenarians alive in 2020 (almost double the figure in 2002), according to the Office for National Statistics. But becoming eligible for a birthday letter from the Queen is still a remarkable feat. We spoke to longevity experts about the science that might help all of us get there and the misconceptions about ageing you should stop believing.

Myth: Theres an evolutionary reason for ageing

To figure out how to slow (or even stop) ageing, we need to know why our bodies do it in the first place. But biologist Cathy Slack from Aston University, says scientists just arent sure yet. From a purely theoretical perspective, theres no beneficial reason to age, she says. We used to think ageing resulted from a buildup of reactive oxygen species (free radicals) which caused molecular damage, but recent research suggests this is unlikely to be the full story. The current most popular explanation is that ageing is an unwanted side effect of biological processes that promote growth and reproduction in our younger years, says Slack.

After a certain point, the same mechanisms that once made us fitter start making us sicker and the body fails to turn them off. Scientists call this the hyperfunction theory of ageing. Its like a tap being left on, says Slack. You need to fill the bath, but if you leave the tap on, the water overflows and you flood your bathroom.

Myth: Old age automatically means poor health

Findings from Perls study of centenarians showed the pianist and the tailor werent outliers. People who make it to 100 arent just long-living, they tend to avoid serious illness until the final chapter of their lives. His participants medical histories suggest there are three broad categories of centenarian. Around 43 percent are delayers who dont exhibit age-related diseases until they reach their eighties. Another 42 percent are survivors who live with chronic disease from their 60s and 70s but it doesnt kill them. The remaining 15 percent or so are escapers - those with no clinically demonstrable disease at 100 years and over.

Its true that age is a major risk factor for many serious illnesses such as heart disease, dementia and diabetes. But Perls believes the old adage the older you get, the sicker you get is false. He prefers to think of it as the older you get, the healthier youve been.

Myth: Theres nothing you can do to prevent death

Its likely that centenarians, and especially super-centenarians (people who live to 110 and over) have genetic variants which protect them from age-related disease, says Perls. But genetics isnt the full picture when it comes to longevity. In fact, research suggests only about 25 per cent of the variation in human lifespan is down to genes. Health-related behaviours and the environment make up the lions share.

Just look to Californias Seventh Day Adventists, says Perls. People from this Christian denomination tend to live up to a decade longer than the average Californian. They dont smoke, drink, or eat meat, which might explain it. Perls thinks most of us could make it into our nineties simply by following a reasonably healthy lifestyle from middle age.

Nutritional epidemiologist Frank Hu, from Harvard TH Chan School of Public Health, agrees. His research, published in the British Medical Journal in 2020, uncovered five lifestyle factors that could gift you ten extra years of life. People whod never smoked, didnt drink much, had a normal BMI, exercised for around 30 minutes a day, and ate a high-quality diet expanded not only their lifespan but also the number of years they lived without serious diseases, such as diabetes, heart disease and cancer. The findings are cause for optimism, says Hu. You dont need to go vegan or run a marathon. Small healthy tweaks might extend your life significantly.

Stopping senescence could be key to living long

Other longevity research zooms in on a type of cell that accumulates in our tissues as we get older. These cells no longer multiply, but they also refuse to die. Biologists once dismissed these zombies, called senescent cells, as irrelevant to health and disease. But some researchers now believe manipulating them could be key to better ageing. Biochemist Judith Campisi from the Buck Institute for Research on Aging in California found senescent cells ooze inflammatory proteins that damage tissue and halt surrounding cells from carrying out their normal processes. Removing them from the body might therefore slow down age-related decline.

In James Kirklands laboratory at Mayo Clinic, Minnesota, mice given drugs called senolytics, which selectively kill these senescent cells, survived for longer than normal and showed delayed onset of multiple conditions usually associated with ageing. Several biotech companies, such as Unity Biotechnology, have since set their sights on senolytics as a potential fountain of youth.

Continued here:
The science that could help you live to 100 - Wired.co.uk