Cellectis Presents Pre-Clinical Evidence of MUC1 CAR T-cells Reducing Triple-Negative Breast Cancer While Preserving Safety

September 3^rd, 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 a scientific article in Science Advances suggesting that TALEN®-edited MUC1 CAR T-cells could be a potential treatment option for advance-stage triple negative breast cancer (TNBC) patients with limited therapeutic options.

Globally, breast cancer continues to be the most prevalent malignancy in women. Among all subtypes, triple-negative breast cancer (TNBC) stands out as the most aggressive form with high metastatic potential and poor survival rates.

Despite a few emerging targeted therapies under investigation, surgery, chemotherapy and radiation therapy continue to be the standard of care, and their success remains limited. As an alternative, Chimeric Antigen Receptor (CAR) T-cell therapies could hold promise for advance-stage TNBC patients as tumor-associated MUC1 antigen is overexpressed in a large number of patients thus offering a distinct target for treatment.

In this article, Cellectis described its multi-layered CAR T-cell engineering strategy using TALEN® and synthetic biology to multi-armor CAR T-cells with synergistic functionalities to overcome the immunosuppressive tumor microenvironment (TME) of solid tumors. With this strategy, Cellectis demonstrates enhanced cytotoxic activity of MUC1 CAR T-cells armored with PD1KO, tumor-specific IL12 release and TGFBR2KO attributes, all of them catered towards the TNBC TME, in intravenous and intratumoral mouse models.

“Complexity of solid tumors decreases the efficacy of CAR T-cell therapies. With this pre-clinical study, we showed that TALEN®-mediated multiplex editing can support CAR T-cells in effectively mounting an anti-tumor response to clear breast tumors, and that we can further decrease the dose of the treatment by injecting the CAR T cells intratumorally while still treating distant tumors. This innovative approach also allowed us to discover an unexpected cooperation between the edits in increasing safety, highlighting the potential capabilities of multiplex editing” said Piril Erler, PhD, Scientist II at Cellectis.

Importantly, intratumoral treatment effectively reduced local and distant tumors of large size using low doses of multi-armored MUC1 CAR T-cells. This pre-clinical data suggests that the benefits of antigen recognition are maintained at distant sites and highlights the potential to address metastasis with local administration.

The article is available on Science Advances’ website by clicking on this link: https://www.science.org/doi/10.1126/sciadv.adn9857