iPSC-derived T cells and macrophages: Manufacturing and next-generation application approaches

Chimeric antigen receptor (CAR) technology has transformed the immunotherapy field with significant success in the treatment of hematological diseases. Nonetheless, challenges in scalability, donor variability as well as in the treatment of solid tumors warrants innovative solutions. Induced pluripotent stem cell (iPSC) technology has revolutionized the filed as an emerging renewable source for CAR-based therapies, facilitating the development of off-the-shelf immune cells products. This review focuses on the recent developments of iPSC-derived CAR-T cells and CAR-macrophages, including differentiation protocols, gene engineering strategies and mitigation of Graft- versus -Host Disease (GvHD), as well as alternatives for histocompatibility constraints. Additionally, we will discuss how iPSC-derivation enhances accessibility of low-frequency immune cell populations including MR1-restricted αβT, γδT, Natural Killer T (NKT) and Microglial cells. Despite great progress achieved, the limited but continuously growing clinical experience and manufacturing challenges, warrant further exploration. Advancements in manufacturing scalability and genetic engineering position iPSC-based therapies at the forefront of clinical strategies to address unmet clinical needs in cancer treatment.