Cellectis Explores Novel CAR T-Cell Therapy for Solid Tumors

Biotechnology firm Cellectis has revealed preclinical findings outlining a new CAR T-cell therapy paradigm aimed at treating stroma-rich solid tumors. The study, published in Frontiers in Immunology, details the use of FAP UCART cells to deplete cancer-associated fibroblasts (CAFs) and modify the tumor microenvironment.

While CAR T-cell therapy has shown success in certain cancers, its efficacy against solid tumors has been limited due to the dense stromal tissue and immunosuppressive conditions that hinder T-cell infiltration and function. Cellectis utilized its TALEN® gene-editing platform to engineer immune-evasive UCAR T-cells targeting the Fibroblast Activation Protein (FAP) marker found on CAFs.

Preclinical results in a mouse model indicated that FAP UCART cells significantly reduced tumor growth. The treatment also reprogrammed the tumor microenvironment, making it more receptive to subsequent CAR T-cell therapy targeting tumor antigens. When combined with a PD-1 checkpoint inhibitor, the treatment achieved maximal antitumor activity and improved survival.

"Over 90% of epithelial cancers express the FAP marker, making it a promising target for CAR T-cell therapy," stated Shipra Das, Senior Scientist & Team Leader at Cellectis. "We propose a novel and versatile combination CAR T-cell therapy approach that can be extended to most stroma-rich, cold tumors that are otherwise recalcitrant to cell therapy."

The research suggests an alternative treatment strategy for aggressive solid tumors that have historically resisted current cell therapies.