Cellectis Presents Multiple Strategies to Enhance CAR T-cell Efficacy in Solid Tumors at the SITC Annual Meeting

New York, NY - November 5, 2024 - 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, announced today that pre-clinical data to enhance CAR T cell activity against solid tumors while preventing potential toxicity, will be presented at the Society for Immunotherapy of Cancer's 39th Annual Meeting (SITC), that will take place on November 6-10, 2024 in Houston, Texas.

The data will be presented in a poster:

Title: Breaking barriers in solid tumors with SMART allogeneic CAR T-cells

Date / Time: November 9th, 2024 from 9:00am to 8:30pm ET

Presenter: Beatriz Aranda-Orgilles, Associate Director, Immuno Oncology at Cellectis

Poster number: 254

Despite the success of CAR T-cell therapies treating blood cancers, these cutting-edge technologies continue to face obstacles in solid tumors. A main barrier is the hostile tumor microenvironment (TME), which forms an immunosuppressive barrier and restricts T-cell infiltration into the tumor. Other contributing causes such as tumor antigen diversity or low expression of CAR-targeted tumor-associated antigens (TAA) in normal tissues can lead to antigen escape or on-target off-tumor toxicity, respectively. These factors can lead to relapse and pose a challenge for therapeutic safety.

Cellectis presents several strategies using TALEN®-mediated gene editing to generate allogeneic CAR T-cells while repurposing PD-1 function with tightly regulated functionalities, with the objective to increase efficacy and avoid potential toxicities in solid tumors.

Using in vitro and in vivo techniques, we show that TME-induced FAP-dependent expression of CAR tethers cytotoxic activity to the tumor area and can minimize potential "on-target off-tumor" toxicities. In a parallel approach, we integrate IL-12 into PD-1 regulatory elements to confine IL-12 to the TME and inactivate TGFBR2 to overcome TGFB1-mediated resistance. This strategy enhances proliferation and infiltration of CAR T-cells, while reducing tumor burden and limiting side effects.

Overall, our data show the potential of repurposing immune pathways to create armored allogeneic CAR T-cells with enhanced activity in immunosuppressive microenvironments while minimizing potential safety issues. These approaches have the potential to provide a therapeutic option for patients with solid malignancies.

The poster is available on Cellectis website