scFv(EGFR)-OX40-CD3zeta CAR-T Lentivirus

The scFv(EGFR)-OX40-CD3ζ CAR-T lentivirus is a cutting-edge viral vector system designed to deliver second-generation chimeric antigen receptor (CAR) constructs to T cells. This lentiviral vector leverages the inherent advantages of lentiviral delivery, including high transduction efficiency in both dividing and non-dividing cells, stable genome integration for sustained CAR expression, and good safety profile due to its self-inactivation (SIN) design, which minimizes the risk of insertional mutations. Pseudogenization of the vesicular stomatitis virus glycoprotein (VSV-G) broadens cell tropism, enabling efficient transduction of primary human T cells. Crucially, this CAR construct integrates an anti-EGFR single-chain variable region fragment (scFv) for precise tumor targeting, incorporates OX40 (CD134) as a co-stimulatory domain to enhance T cell persistence, and CD3ζ for initial activation signaling. This synergistic design enhances anti-tumor activity while reducing T cell exhaustion, resulting in more durable therapeutic effects compared to first-generation CARs.

The application of this CAR-T lentivirus is primarily focused on adoptive immunotherapy for EGFR-expressing malignancies, including glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and colorectal cancer. After transduction, T cells can independently recognize EGFR-overexpressing tumor cells, bypassing common immune escape mechanisms. The OX40 co-stimulatory domain is particularly important in the solid tumor microenvironment, combating immunosuppressive factors by promoting T cell survival, memory differentiation, and metabolic adaptation. In preclinical models, this construct exhibited stronger tumor clearance and more durable immune memory compared to CD28-based CARs. Beyond oncology, this platform can serve as a versatile tool for immunological research, facilitating studies on T cell signaling dynamics, tumor microenvironment interactions, and drug resistance mechanisms.