NEW YORK, May 12, 2023 (GLOBE NEWSWIRE) – Cellectis (the “Company”) CLLSa clinical-stage biotechnology company using its breakthrough gene-editing platform to develop life-saving cell and gene therapies, today published an article in Frontiers Bioengineering demonstrating the efficacy of its TALEN® engineered FAP-UCART cells in cancer-associated fibroblasts will ( CAF) depletion, reduction of desmoplasia and tumor infiltration.

Chimeric antigen receptor engineered T cell (CAR-T) adoptive cell therapy has proven life-saving for many cancer patients.

However, its therapeutic effectiveness has so far been limited to only a few malignant diseases, with solid tumors proving to be particularly resistant to efficient therapy. Poor infiltration of T cells into the tumor and T cell dysfunction due to a desmoplastic, immunosuppressive microenvironment are major obstacles to the success of CAR T cells in fighting solid tumors.

Cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma and develop specifically within the tumor microenvironment (TME). The CAF secretome makes a major contribution to the extracellular matrix and a variety of cytokines and growth factors that induce immunosuppression. Together they form a physical and chemical barrier that induces a T cell-exclusive “cold” TME. CAF depletion in stromal-rich solid tumors may therefore provide an opportunity to convert immune-vasive tumors susceptible to tumor antigen-CAR T-cell cytotoxicity.

Cellectis used its TALEN®-based gene-editing platform to engineer non-alloreactive, immune-vasive UCAR-T cells that target the unique CAF marker Fibroblast Activation Protein, Alpha (FAP) to test whether a FAP -UCAR-T cell pre-treatment “Cold tumors susceptible to subsequent tumor antigen-targeting CAR-T cells. Cellectis also generated non-alloreactive CAR-T cells against the tumor-associated antigen (TAA) mesothelin, which is overexpressed in most solid tumors, including mesothelioma and large subgroups of….