On June 30, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that research data on its novel immune-evasive universal CAR T-cells in Nature Communications, following an oral presentation at the American Society of Cell and Gene Therapy (ASGCT) (Free ASGCT Whitepaper) on May 16 (Press release, Cellectis, JUN 30, 2022, View Source [SID1234616406]).

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Cellectis’ next generation of universal CAR T-cells have the potential to improve the persistence and to allow large-scale deployment of T-cell product candidates in allogeneic settings against multiple malignancies.

Universal CAR T-cell therapies are poised to revolutionize the treatment of selected hematologic malignancies. However, realizing the full potential of CAR T in an allogeneic setting requires universal CAR T-cells that can kill target tumor cells, avoid depletion by the host immune system via the host versus graft reaction (HvG), and proliferate without attacking host tissues via the graft versus host reaction (GvH).

While the prevention of GvH can be readily addressed by the inactivation of T cell receptor T αβ (TCRαβ) expression in a CAR T-cell, prevention of HvG remains a major challenge.

To address this challenge, the Cellectis investigators engineered CAR T-cells to be deficient in Class 1 major histocompatibility complex (MHC-1) and to express the Natural Killer (NK) inhibitor HLA-E, in order to endow them with immune-evasive properties toward alloreactive Tc ells and NK cells.

"This engineering approach is very promising and could enable the universal CAR T-cells to become transiently invisible to NK and alloreactive T-cells, allowing them to eradicate tumor cells before being rejected by the patient’s immune system. This could enable the broad use of universal CAR T-cells in allogeneic settings, for the benefit of a wider population of patients." said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis.

"One potential advantage of this approach is to spare endogenous immune effectors and allow them to work in concert with CAR T-cells in the fight against hard-to-treat cancers, including solid tumors" said Laurent Poirot, Ph.D. Senior Vice President Immuno-Oncology at Cellectis.

The research data show that:

· Endowing universal CAR T-cells with immune-evasive properties via TALEN-mediated gene editing and adeno-associated virus (AAV)-dependent gene insertion, is highly efficient and specific, transferable to different CAR constructs and adaptable to conventional CAR T-cell manufacturing processes.

· Immune-evasive universal CAR T-cells overcame alloresponsive T-cell and NK cells attacks and exhibit prolonged antitumor activity, even in the presence of highly active NK cells.

· Immune-evasive properties against NK cells from most healthy donors and acute myeloid leukemia (AML) patients were similar, demonstrating the robustness and transportability of this hypoimmunogenic approach to persistence and warranting further evaluation in preclinical and clinical settings