Abstract
Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy. This review elucidates molecular mechanisms and therapeutic potential of next-generation immunotherapeutic tools spanning genetically engineered immune cells, multi-specific antibodies, and cell engagers, emphasizing multi-targeting strategies to enhance personalized immunotherapy efficacy. Development of logic gate modulation-based circuits, adapter-mediated CARs, multi-specific antibodies, and cell engagers could minimize adverse effects while recognizing tumor signals. Ultimately, we highlight gene delivery, gene editing, and other technologies facilitating tailored immunotherapy, and discuss the promising prospects of artificial intelligence in gene-edited immune cells.