scFv(CD38)-CD28-OX40-CD3zeta CAR-T Lentivirus

The single-chain variable region (scFv) is derived from an antibody that recognizes CD38, a surface marker commonly overexpressed in multiple myeloma and various hematologic malignancies. Incorporating the scFv into the CAR construct enables T cells to specifically recognize and bind to CD38-presenting cancer cells, thereby improving targeting accuracy and therapeutic potential. CD28 signaling is crucial for T cell activation, survival, and proliferation. By incorporating this domain, CAR-T cells are not only activated upon binding to the CD38 antigen but also receive important survival signals, enhancing their persistence and function within the tumor microenvironment.

In addition to CD28, the OX40 costimulatory domain is also part of the CAR design. OX40 enhances T cell responses and promotes the formation of long-term memory T cells. This dual costimulatory approach, combining CD28 and OX40, is designed to maximize T cell activation, tolerance, and overall anti-tumor efficacy. The presence of two costimulatory signals is crucial to overcoming the immunosuppressive tumor microenvironment, which cancer cells often exploit to evade immune responses. The third key component of this CAR is the CD3ζ signaling domain. CD3ζ is essential for T cell receptor signaling and plays a crucial role in activating T cell responses. It facilitates the transmission of activation signals upon T cell engagement, leading to cytokine release and cell proliferation. Lentiviral vectors are used in the engineering of CAR-T cells because they can integrate into the host genome, ensuring stable and continuous expression of the CAR construct within T cells. This results in a long-lasting immune response that effectively targets and eliminates CD38+ cancer cells even after initial treatment.