Chimeric antigen receptor cell therapies: From anticancer immunity to tissue repair and neural regeneration

Originally developed as breakthroughs in cancer immunotherapy, Chimeric antigen receptor cell therapies have recently attracted attention because of their potential to promote tissue repair and functional restoration. This review examines the emerging role of chimeric antigen receptor-engineered immune cells, particularly chimeric antigen receptor T cells and chimeric antigen receptor-natural killer cells, in facilitating tissue repair, modulating inflammatory microenvironments, and supporting neural regeneration. Unlike conventional approaches that directly deliver growth factors or stem cells, chimeric antigen receptor cells can be reprogrammed to eliminate senescent cells, resolve chronic inflammation, and remove damaged extracellular matrix components, thereby creating a pro-regenerative niche. First, we summarize the structural evolution of chimeric antigen receptors across five generations and compare the distinct mechanisms of adaptive (chimeric antigen receptor T cells) and innate (chimeric antigen receptor-natural killer) immune killing. Second, we highlight preclinical and clinical evidence that chimeric antigen receptor T cell and chimeric antigen receptor-natural killer cell therapies can accelerate wound healing, reduce fibrotic scarring, and support axon regrowth after central nervous system injury. Key challenges—including on-target/off-tumor toxicity, immune exhaustion, and poor infiltration into solid tissues—are discussed alongside engineering solutions such as logic-gated chimeric antigen receptor, chemokine receptor co-expression, and local delivery strategies. Finally, we outline future directions for integrating chimeric antigen receptor technology into combinatorial regenerative protocols, including in situ reprogramming and synthetic biology-driven feedback control. Repurposing the cytotoxic precision of chimeric antigen receptor cells toward non-malignant targets holds promise for treating degenerative diseases, chronic wounds, and traumatic neural injuries where immune dysregulation impedes natural repair.