Carisma Therapeutics (CARM) announced positive pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte, or CAR-M, therapy for hepatocellular carcinoma, or HCC, developed in collaboration with Moderna (MRNA). The data demonstrated that the development candidate can successfully create CAR-M directly in vivo, reprogramming endogenous myeloid cells to target and destroy Glypican-3, expressing cancer cells. Pre-clinical results showed that the novel in vivo anti-GPC3 CAR-M therapy exhibits specificity for the GPC3 tumor antigen, driving potent dose-dependent cytotoxicity against GPC3+ tumor cells. Additionally, the CAR-M produced pro-inflammatory cytokines and adopted an inflammatory, activated macrophage phenotype upon antigen engagement. 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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