scFv(CD38)-CD28-41BB-CD3zeta CAR-T Lentivirus

CAR-T cells, which use genetic modification to transfer genetic material containing specific antigen recognition domains and T cell activation signals into T cells, enable direct binding of T cells to specific antigens on the tumor surface, achieving precise targeted therapy. First-generation CARs lack co-stimulatory molecules for T cell activation, resulting in low T cell proliferation and cytokine release. This results in inefficient CAR-T cell activation and, consequently, poor clinical efficacy. Second-generation CARs build on the first-generation approach by adding an intracellular immunoreceptor tyrosine-based activation motif (ITAM) region derived from the co-stimulatory molecules CD28 or CD137 (4-1BB). Upon binding to the target antigen, the T cell receives both antibody stimulation and co-stimulatory signals. Consequently, second-generation CARs possess significantly greater activation and cytotoxicity than first-generation CARs and have demonstrated promising clinical efficacy. Due to their high stability and mature technology, they are currently the mainstream technology.

Third-generation CARs further enhance CAR-T cell efficacy by adding two or more co-stimulatory signaling domains, such as CD28, CD137, or CD134 (OX40). Fourth-generation CARs enhance CAR-T efficacy through genetic modification to secrete cytokines or express co-stimulatory ligands. Suicide genes or drug-sensitizing genes can also be added to reduce cytotoxicity when necessary. Currently, these technologies are in the preclinical research stage. As new third- and fourth-generation CAR structures are introduced into clinical trials, their efficacy is highly anticipated.