Next-generation CAR-T cell engineering by Chinese scientists: Structural innovation, tumor microenvironment remodeling, and clinical translation.

Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a transformative modality in cancer immunotherapy. While global efforts have advanced the field, China has played a pivotal role in shaping the development and clinical deployment of CAR-T technologies. We, herein, provide a comprehensive evaluation of China's contributions in structural refinements, the antigen-binding domain and intracellular signaling modules of CAR. Moreover, Chinese preclinical studies have addressed on enhancing T cell infiltration, overcoming immune checkpoint resistance, and remodeling the tumor microenvironment. We, further, review the discovery of novel targets, strategies to minimize on-target/off-tumor toxicity, and innovative manufacturing approaches that have optimized product quality and reduced costs. Clinical translation efforts in China have accelerated rapidly, supported by a robust research infrastructure and regulatory framework, leading to a growing portfolio of CAR-T cell products in trials and practice. Future research should focus on enhancing CAR-T cell efficacy against solid tumors, integrating gene editing technologies, and expanding allogeneic platforms for scalable, off-the-shelf therapies.