Carisma Therapeutics Inc. (Nasdaq: CARM) (“Carisma” or the “Company”), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, today announced positive pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte (together, “CAR-M”) therapy for hepatocellular carcinoma (“HCC”), developed in collaboration with Moderna, Inc. (Nasdaq: 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 (“GPC3”), 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.
“The data demonstrate our ability to generate anti-GPC3 CAR-M cells directly in vivo using mRNA/LNP technology, leading to significant tumor reduction in translationally relevant pre-clinical models,” said Michael Klichinsky, PharmD, PhD, Co-Founder and Chief Scientific Officer at Carisma. “This novel off-the-shelf approach offers a promising new strategy for treating hepatocellular carcinoma, and we are eager to advance it toward clinical development.”
“These preclinical data highlights the successful application of our mRNA/LNP platform in enabling in vivo cell therapy,” said Lin Guey, PhD, CSO of Therapeutic Research Ventures, Moderna. “We look forward to further advancing the anti-GPC3 in vivo CAR-M therapy for HCC patients and continuing our collaboration with Carisma to bring innovative treatments to those patients with solid tumors.”