Genome editing specialist Cellectis has kicked off clinical tests in the US for the very first of-the-shelf CAR-T cell therapy in acute myeloid leukaemia.

The company said it enrolled the first patient with acute myeloid leukaemia (AML) to be treated with UCART123 at Weill at Cornell Medicine, New York Presbyterian Hospital. UCART123 is a TALEN-genome edited chimeric T cell receptor targeting the CD123/IL3R antigen on the surface of blasts and dendric cells, which is administered on allogeneic donor T cells. The team of Gail J. Roboz will investigate the safety and will collect first indications for efficacy of UCART123 in patients with AML. The Phase I trial is part of a strategic translational research alliance that was formed between Cellectis and Weill Cornell Medicine in 2015.

While Novartis AG and Kite Pharma are leading the CAR-T cell therapy development in AML, Cellectis hopes to overtake its competitors. It has the only approach that works with allogenic CAR-engineered T cells that could be centrally pre-manufactured in contrast to the autologous patient T cells. Those need to be isolated, engineered and expanded during the at least 14 day hospital stay of the patients to be treated making the procedure costly, lengthy and laborious. On the other hand, Cellectis therapy does not target the CD19 T cell antigen but CD123//IL3R giving the company another unique selling point.

Cellectis has used TALEN technology to block expression of the TCRa constant (TRAC) gene though blocking expression of the natural TCR. According to Andr Choulika, Cellectis CEO, TALEN technology shows less off-target effects compared to CRISPR/Cas9 genome editing. Following apheresis, donor T cells are engineered to express an anti-CD123 CAR (CD123 scFv-41BB-CD3z) and an RQR8 depletion ligand that confers susceptibility to rituximab. Theoretically, specifity of of UCART123 therapy might be higher in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) than in patients with AML as CD123 expression is 10fold higher in the precursors of plasmacytoid dendritic cells than in blast occurring in the course of AML.

Cellectis also announced two new entries to ists Board of Directors. Ex-Novartis pharma division head Rainer Boehm will lead commercialisation of Cellectis lead candidate. Ex Novartis Oncology President and Incyte Corp CEO Herv Hoppenot will lead clinical development.

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AML: Cellectis testing allogenic CAR-T cell therapy - European Biotechnology