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Cellectis presents way to safer CAR-Ts

15.11.2019
by tg

Researchers at French-US allogeneic CAR-T cell developer Cellectis SA have designed an engineered CAR-T cell that secretes IL-12 upon contact with tumour cells.

The company presented the in vitro "proof-of-concept" of their new CAR-T cells, in which they integrated a gene network that senses tumour cells and secretes the proinflammatory cytokine IL-12 as a reaction, in Nature Communications. Specifically, the team headed by Julien Valton inserted several major players of the T cell activation pathway into T cells: firstly, the CAR into the TCRαlpha gene (TRAC_CAR), second IL-12P70 into either IL2R-alpha or PDCD1 genes. The construct transiently secreted IL-12P70 depending on the concentration of tumour antigen, showed increased TRAC_CAR T cell cytotoxicity and extended survival of tumour-xenografted mice. "This engineering strategy could bring smarter, safer and more effective treatments to the forefront for patients in need,” commented Valton.

“Discussion around the tumor microenvironment has become a popular topic in the CAR T-cell space, and with recent advancements in gene editing technologies, especially TALEN^®, it is now possible to manipulate the way a T-cell regulates itself to adapt to its environment,” said Dr. Philippe Duchateau, Ph.D., Chief Scientific Officer at Cellectis. The company develops gene-edited allogeneic CAR T-cells (UCART), that might cause no or reduced dosing of immunosuppressants.

German Rheincell GmbH, however, is preparing to reduce the need for immunosuppression after cell transplantation without any genetic engineering. Two years after its launch, the start-up company has started to build a GMP-compliant iPSC (induced pluripotent stem cell) master cell bank with homozygous HLA antigens that match most acceptors and from which any cell type needed for cell therapies can be derived.

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