Multicenter phase 1 trial of CAR-macrophage therapy for HER2-overexpressing advanced solid tumors

Chimeric antigen receptor macrophages (CAR-Ms) mediate antitumor immunity via phagocytosis, cytokine release, activation of the tumor microenvironment and antigen presentation. A multicenter phase 1 trial in the United States evaluated CT-0508, an anti-HER2 CAR-M in patients with advanced HER2-overexpressing tumors. No lymphodepletion chemotherapy was used before infusion. No dose-limiting toxicities, grade ≥ cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome were observed. Among patients with HER2 IHC 3+ tumors, stable disease as best overall response 8 weeks after treatment was seen in 44% (95% CI 14-79). No meaningful activity was observed in the HER2 2+ population. Correlative analyses of serial biopsies confirmed that CT-0508 traffics to the tumor environment, resulting in expansion of CD8⁺ T cells. The authors conclude that these findings demonstrate the preliminary safety, tolerability, and manufacturing feasibility of CT-0508 for HER2⁺ tumors.