[Establishment of hPSC derived CAR-macrophage and its application in solid tumors]

Immunotherapy, in particular, chimeric antigen receptor T cells (CAR-T), is known as a critical approach for the treatment of patients with hematological malignancies. However, there are still huge challenges in the treatment of solid tumors. Therefore, further studies are required to the application of CAR technology to other types of immune cells, for example, CAR-macrophages (Mϕ). Human pluripotent stem cells (hPSC) can be genetically modified either by viral and non-viral methods at clonal level and efficiently differentiate into Mϕ. Therefore, hPSC provide an important platform to produce large scale of genetically engineered Mϕ. CAR engineering Mϕ can enhance the targeted recognition ability, antigen presentation function, cytokine secretion and immune cell recruitment, thereby improving its anti-tumor activity. In the current review, we summarize the current methods for differentiating hPSC into Mϕ, the engineering strategies of CAR-Mϕ, and the current antitumor applications to treat solid tumors. Meanwhile, we focus on the application prospects and challenges of hPSC-derived CAR-Mϕ in solid tumors. Furthermore, we comprehensively analyze the potential of CAR-Mϕ in the field of cell therapy, and deeply explore the unique advantages of Mϕ. This review might provide the potential ideas and new directions for future research and application.