CARISMA Therapeutics Announces FDA Fast Track Designation for CT-0508, a First-in-Class CAR-M Therapy Targeting HER2-Positive Solid Tumors

On September 22, 2021, Carisma Therapeutics announced that the U.S. FDA has granted Fast Track designation to the cell therapy CT-0508. CT-0508 is a chimeric antigen receptor macrophage (CAR-M) therapy targeting human epidermal growth factor receptor 2 (HER2) for the treatment of patients with solid tumors.

CAR-T cell therapy has demonstrated remarkable efficacy in treating hematologic malignancies, yet it has not achieved comparable results in solid tumors. This is largely attributable to the tumor microenvironment and the high heterogeneity of solid tumors. Solid tumors establish an immunosuppressive tumor microenvironment that impedes the infiltration of T lymphocytes. Even when some T lymphocytes manage to infiltrate the tumor, their immune responses may still be restricted by immunosuppressive cells or inhibitory factors within the microenvironment. Furthermore, the high heterogeneity of solid tumors limits the efficacy of CAR-T therapies targeting a single antigen.

CT-0508 was initially co-developed by the co-founders of Carisma Therapeutics, Professor Saar Gill and Dr. Michael Klichinsky at the University of Pennsylvania. In a study published in Nature Biotechnology, they found that expressing chimeric antigen receptors (CARs) targeting tumor antigens on macrophages could transform these cells into "cellular weapons" against solid tumors. This therapy, known as CAR-M, successfully reduced tumor burden and prolonged survival in mouse models of HER2-positive metastatic ovarian cancer.

Genetically engineered macrophages not only express a CAR targeting the HER2 antigen but are also activated and polarized into the pro-inflammatory M1 macrophage phenotype. Consequently, these CAR-M cells can not only specifically target and phagocytose tumor cells, but also remodel the local tumor microenvironment by secreting pro-inflammatory cytokines. Furthermore, they can present tumor antigens to T cells, thereby activating T cell-mediated anti-tumor immune responses, effectively delivering a threefold therapeutic benefit.

CT-0508 is currently undergoing a Phase 1 clinical trial. Eligible subjects are patients with recurrent or metastatic HER2-overexpressing solid tumors for whom no approved HER2-targeted therapy is available, or for whom current treatment is ineffective.

References:

[1] CARISMA Therapeutics Announces U.S. Food and Drug Administration Grants Fast Track Designation to CT-0508 for the Treatment of Patients with Solid Tumors. Retrieved September 22, 2021, from https://www.prnewswire.com/news-releases/carisma-therapeutics-announces-us-food-and-drug-administration-grants-fast-track-designation-to-ct-0508-for-the-treatment-of-patients-with-solid-tumors-301381843.html

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