This paper discusses the emerging field of engineering myeloid cells, specifically macrophages, for cancer immunotherapy. It begins by contrasting the promising but challenging Chimeric Antigen Receptor T-cell (CAR-T) therapies, which face issues like toxicity and limited efficacy against solid tumors, with alternative approaches like CAR-Natural Killer (CAR-NK) cells and CAR-macrophages (CAR-Ms). The commentary primarily explores the potential of CAR-Ms to overcome the limitations of CAR-T cells, noting their improved safety profile-exhibiting only low-grade cytokine release syndrome (CRS) in initial human trials-and their natural ability to infiltrate solid tumors and modulate the tumor microenvironment (TME). Furthermore, the source highlights that CAR-Ms kill tumor cells via CAR-dependent phagocytosis and can induce endogenous anti-tumor T cell responses, especially when combined with checkpoint inhibitors like anti-PD-1 or anti-CD47. Finally, it addresses logistical challenges and future directions, emphasizing the development of in vivo gene editing of macrophages as a strategy to create more cost-effective and accessible cancer treatments.

References:

• Chen J, Zhao Y, Chen X, et al. Engineering myeloid cells for cancer immunotherapy[J]. Cancer Cell, 2025, 43(9): 1593-1597.