Advances in CAR-T Cell Therapy: From Structural Design Innovations to Clinical Translation Challenges.

Chimeric Antigen Receptor T cells (CAR-T) therapy represents a groundbreaking technology in the field of tumor immunotherapy. This innovative approach involves the genetic engineering of T cells to specifically identify and eradicate tumor cells, and it has been shown to yield remarkable efficacy in treating hematological malignancies. This article provides a comprehensive overview of the core advancements in CAR-T technology, emphasizing the evolution of the five generations of CAR structures. Furthermore, it explores the latest innovations in transfection techniques, highlighting optimizations and comparative advantages of viral and non-viral vectors. The future of CAR-T therapy is poised to focus on several validated translational directions: the development of universal off-the-shelf CAR-T cell products, the design of multi-target and logic-gated intelligent CAR architectures, innovative in vivo genetic reprogramming platforms, and synergistic combinatorial therapeutic regimens to overcome solid tumour immune suppression. These advancements aim to enhance the specificity, safety, and accessibility of CAR-T therapies. This article seeks to outline the current state of CAR-T technology while providing insights into potential theoretical frameworks and technical pathways for its future evolution.