Lifespan-Regulated CAR-Macrophages from Myeloid Progenitors for Enhanced Colorectal Cancer Therapy.

ABSTRACT: Adoptive cell therapies for solid tumors face persistent challenges from poor tumor infiltration and immunosuppressive microenvironment. To overcome these limitations, a clinically scalable platform is developed to generate chimeric antigen receptor macrophages (CAR-HMs) from tamoxifen-regulated immortalized Hoxb8-transduced myeloid progenitors, achieving >95% CAR transduction efficiency and 60-fold expansion within 10 days. Engineered with a colorectal cancer-specific anti-carcinoembryonic antigen (CEA) CAR, these FcγRI-CAR-HMs demonstrated potent tumoricidal activity (>80% CRC cell lysis in vitro), deep tissue penetration (>100 µm in 3D tumor spheroids), and significant therapeutic efficacy (≈89% tumor regression in vivo). Mechanistic studies demonstrated that FcγRI-CAR-HMs remodeled the

SUBMITTER: Gao C 

PROVIDER: S-EPMC12631822 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature