On February 24, 2025 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 an innovative strategy for T cell engineering that leverages the pro-inflammatory properties of interleukin 2 (IL-2) with the objective to enhance CAR T cell efficacy against solid tumors, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) – Immuno-oncology (AACR-IO), taking place on February 23-26, 2025 in Los Angeles, CA (Press release, Cellectis, FEB 24, 2025, View Source [SID1234650466]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The data are presented in a poster:
CAR induced expression of synthetically engineered FAP-IL2v immunocytokine boosts persistent anti-tumor activity of TALEN-edited allogeneic CAR T-cells without associated IL-2 toxicity
Presenter: Shipra Das, Ph.D., Associate Director Immuno-Oncology, at Cellectis.
Date/Time: February 25, 2025, 1:45-4:45 p.m. PT
Session: Poster Session B
CAR T-cell therapies have transformed the treatment landscape for specific hematological malignancies and have shown promising preliminary efficacy in solid tumors.
Recent studies suggest a link between the in vivo expansion and persistence of CAR-T cells and enhanced therapeutic outcomes in patients. The co-administration of interleukin-2 (IL-2) has been demonstrated to improve CAR T-cell engraftment, expansion, and functionality in preclinical models but poses toxicity risks at high doses.
Using Cellectis’ TALEN gene editing technology, we developed ‘Smart CAR T cells’ with the ability to express a CAR-inducible IL-2 variant (IL-2v) immunocytokine, potentiated by tumor-specific cues for localized activity within the solid tumor microenvironment (TME).
CAR-inducible expression of this recombinant FAPscFv-IL2v boosts anti-tumor activity of engineered CAR T-cells both in vitro and in vivo. Notably, the enhancement of CAR T-cell activity mediated by IL-2v relies on its anchoring to the FAP protein, which is uniquely present in the TME, thus minimizing the systemic toxicity typically associated with circulating free IL-2 cytokines.
This proposed cellular engineering strategy would represent an effective and safe method to substantially improve CAR T cell expansion and anti-tumor activity, while confining IL-2 activity to the tumor microenvironment.