Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy

Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notable advantages, including various sources and diminished toxicity, and are gaining recognition in clinical research. CAR-macrophages (CAR-M), while sharing antigenic domains similar to those of CAR-T cells, display superior capabilities in antigen presentation and tumor penetration. As a result, there is significant enthusiasm surrounding investigations into CAR-NK and CAR-M cell immunotherapies. This review explores the existing environment and obstacles associated with immunotherapies that utilize CAR-T, CAR-NK, and CAR-M cells to inspire novel pathways for forthcoming clinical applications.