Document resource
Background Macrophages possess robust tumor-infiltrating capabilities. Engineered macrophages (chimeric antigen receptor macrophages, CAR-M) with enhanced targeting specificity and the ability to evade immunosuppressive microenvironments represent a groundbreaking advancement in solid tumor therapy. The mentioned CAR-M is a third generation of CAR-M, incorporating a tandem design of cytokine GM-CSF, which is essential for macrophage autonomous proliferation and activation along with the CAR construct. This innovative approach aims to overcome the current therapeutic limitations in solid tumor management.Methods As of June 2025, a total of 7 patients (median age 56) were enrolled, including 3 HER2-positive and 4 HER2-low cases. These patients received CAR-M infusion via intraperitoneal in a dose-escalation manner at one-week intervals. The primary endpoints included evaluating tumor progression status and clinical improvement, as well as calculating ORR, CR, and PR. The secondary endpoint was PFS.Results CAR-M showed favorable safety and tolerability profiles. No DLTs or ICANS were observed during infusion. The incidence of ≥ grade 2 TEAEs was 0. Among the 7 patients, only mild CRS occurred, primarily manifesting as fever and chills, which resolved spontaneously within 48 hours. HER2-positive patients exhibited reduced tumor biomarkers and radiologically confirmed tumor shrinkage. The DCR was 100%, with a 6-month PFS rate of 100%. Notably, 5/7 patients experienced weight gain. HER2-low patients indicated tumor stabilization or regression, achieving a DCR of 50% and a median PFS of 4.6 months. Transient T-cell exhaustion was observed in one case, strikingly, however, immune recovery occurred within one month.Conclusions CAR-M demonstrated a manageable safety profile along with encouraging response rates. Further CAR-M investigations targeting additional antigens are currently being planned.Trial Registration ChiCTR2400082776 and ChiCTR2400080078Ethics Approval Approval Letter of Clinical Research Ethics Committee of The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. ID: XYFY2023-KL107-01 and XYFY2024-KL077-01