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

On 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, reported 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 (SITC) (Free SITC Whitepaper)’s 39th Annual Meeting (SITC) (Free SITC Whitepaper), that will take place on November 6-10, 2024 in Houston, Texas(Press release, Cellectis, NOV 5, 2024, View Source [SID1234647710]).

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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.