Year: 2026
Type: article
Abstract: Chimeric antigen receptor (CAR)-T therapy is limited in solid tumors by poor infiltration and immunosuppression, while myeloid cell translation is hindered by expansion bottlenecks and allogeneic MHC mismatch. Now, Yue et al. establish an expandable granulocyte-monocyte progenitor (GMP) platform that overcomes three long-standing bottlenecks of macrophage-based therapy—poor ex vivo expansion, limited genetic tractability, and short-lived persistence after infusion. Critically, infused GMPs persist long-term in vivo, reconstitute functional myelopoiesis, and restore antibacterial immunity in chronic granulomatous disease (CGD) mice, demonstrating that GMP-derived macrophages are functionally competent. The authors also engineer a CAR-Fc construct that enables both direct phagocytosis and host Fc receptor-mediated trans -phagocytosis. In fully MHC-mismatched immunocompetent models, mature CAR-Fc macrophages mediate a "hit-and-run" effect—transient donor cell persistence coupled with durable host adaptive immunity. These findings redefine the feasibility of allogeneic myeloid cell therapy and provide a transformative roadmap for CAR-microglia against central nervous system (CNS) malignancies.
Source: Immunity & Inflammation
Authors: Jia Xu, Zi-Bing Jin
Institution: Beijing Tongren Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Award: G8769823961
OpenAlex ID: W7221590522