Carisma Therapeutics Inc. announced positive pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte (CAR-M) therapy for hepatocellular carcinoma (HCC) at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. The data, developed in collaboration with Moderna, Inc., demonstrated the therapy's ability to successfully create CAR-M directly in vivo. This process reprograms endogenous myeloid cells to specifically target and destroy Glypican-3 (GPC3) expressing cancer cells.
Pre-clinical results showed that the novel in vivo anti-GPC3 CAR-M therapy exhibited specificity for the GPC3 tumor antigen, driving potent dose-dependent cytotoxicity against GPC3+ tumor cells. The CAR-M also produced pro-inflammatory cytokines and adopted an inflammatory, activated macrophage phenotype upon antigen engagement. These findings support the potential of this off-the-shelf approach.
In both syngeneic and humanized tumor models, systemic administration of anti-GPC3 CAR mRNA/LNP significantly reduced tumor burden and suppressed metastasis to the liver. The therapy was well tolerated in mouse models, highlighting its potential as an off-the-shelf treatment for GPC3+ solid tumors, including HCC.
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