Cellectis Publishes a Molecular Therapy Article on a SMART DUAL CAR T-cell Approach for Treating Recalcitrant Solid Tumors

August 26, 2024 - New York, NY - 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, today published an article in Molecular Therapy demonstrating TALEN® -mediated gene editing capabilities for design of SMART DUAL CAR T-cells, which efficiently target immunotherapy recalcitrant solid tumors while mitigating potential safety risks.

Adoptive cell therapy based on CAR T cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy.

One key factor for this are cancer-associated fibroblasts (CAFs), that modulate the tumor microenvironment (TME) to inhibit T cell infiltration and induce T cell dysfunction. Additionally, the sparsity of tumor-specific antigens (TSA) and expression of CAR-directed tumor-associated antigens (TAA) on normal tissues often results in on-target off-tumor cytotoxicity, raising safety concerns.

Using TALEN® gene editing technology, Cellectis presents an innovative CAR T cell engineering strategy designed to overcome these challenges. Our allogeneic SMART CAR T-cells are designed to express a constitutive CAR, targeting FAP+ CAFs in solid tumors, and a second inducible CAR, expressed only in the presence of FAP+ CAFs and targeting the tumor associated antigen (TAA) named mesothelin. The resultant SMART Dual CAR T-cells efficiently infiltrate and efficiently target triple-negative breast tumors in physiologically relevant mice models, with no observable on-target, off-tumor toxicity.

"The adaptations of this approach could resolve several key challenges for CAR T-cell therapy against solid tumor-low CAR T-cell infiltration, immuno-suppressive microenvironment, antigen heterogeneity as well as on target, off-tumor toxicity. This strategy thus has significant implications for successful therapeutic development of CAR T-cells against solid tumors" said Shipra Das, Ph.D., Associate Director Immuno-Oncology and Innovation Program Management at Cellectis.

The article is available on Molecular Therapy website by clicking on this link : https://www.sciencedirect.com/science/article/pii/S1525001624005409?utm_campaign=STMJ_219742_AUTH_SERV_PA&utm_medium=email&utm_acid=300123771&SIS_ID=&dgcid=STMJ_219742_AUTH_SERV_PA&CMX_ID=&utm_in=DM500444&utm_source=AC_