Cellectis Shows MUC1 CAR T-cells Reduce Triple-Negative Breast Cancer Safely

Cellectis, a clinical-stage biotechnology company listed on Euronext Growth and NASDAQ, has recently published a groundbreaking article in Science Advances. This article delves into the potential of TALEN®-edited MUC1 CAR T-cells as a treatment for advanced-stage triple-negative breast cancer (TNBC), a highly aggressive form of cancer with limited therapeutic options.

Breast cancer remains the most common malignancy among women worldwide, and TNBC is particularly notorious for its aggressive nature, high metastatic potential, and poor survival rates. Standard treatments for TNBC typically include surgery, chemotherapy, and radiation therapy, although their success is often limited. Recently, there has been growing interest in Chimeric Antigen Receptor (CAR) T-cell therapies, which could offer a novel treatment avenue for advanced-stage TNBC. This is particularly relevant as the tumor-associated MUC1 antigen, a potential target for CAR T-cell therapies, is overexpressed in a significant number of TNBC patients.

In its scientific article, Cellectis elaborates on its sophisticated CAR T-cell engineering strategy. Using TALEN® and synthetic biology, the company has developed multi-armored CAR T-cells with various synergistic functionalities aimed at overcoming the immunosuppressive tumor microenvironment (TME) of solid tumors. Through this strategy, Cellectis aims to enhance the cytotoxic activity of MUC1 CAR T-cells. These cells are equipped with PD1KO, tumor-specific IL12 release, and TGFBR2KO attributes. These features are specifically designed to interact with the TNBC TME, both in intravenous and intratumoral mouse models.

Piril Erler, PhD, a Scientist II at Cellectis, commented on the complexity of solid tumors and the challenges they pose to CAR T-cell therapies. She highlighted how TALEN®-mediated multiplex editing can enable CAR T-cells to mount effective anti-tumor responses, thereby clearing breast tumors. Moreover, this approach allows for lower doses of treatment when CAR T-cells are injected directly into the tumor, yet still effectively address distant tumors. This innovative strategy not only boosts the anti-tumor efficacy but also enhances safety, unveiling the potential of multiplex editing.

The pre-clinical data revealed that intratumoral treatment with multi-armored MUC1 CAR T-cells significantly reduced the size of local and distant tumors using low doses. This indicates that the benefits of antigen recognition by CAR T-cells are maintained even at distant sites, suggesting potential applications for addressing metastasis through localized administration.

Cellectis is a company with over 25 years of experience in gene editing. It employs its pioneering TALEN® gene-editing platform to develop life-saving cell and gene therapies. By utilizing an allogeneic approach for CAR T immunotherapies in oncology, Cellectis aims to create off-the-shelf, ready-to-use gene-edited CAR T-cells to treat cancer patients. In addition, the company is working on therapeutic gene editing in hematopoietic stem cells for various diseases. Cellectis operates out of headquarters in Paris, France, and has locations in New York and Raleigh, North Carolina.

The findings from this study promise to open new avenues in the treatment of TNBC, a form of cancer that has long posed significant treatment challenges. The innovative multiplex editing approach discussed in the article could potentially revolutionize the way advanced-stage TNBC is treated, bringing hope to patients who have few therapeutic options.

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