scFv(EGFR)-CD28-CD3zeta CAR-T Lentivirus

Lentiviral particles containing the second-generation anti-EGFR chimeric antigen receptor (CAR) scFv-CD28-CD3zeta represent a cutting-edge viral vector system for CAR-T cell therapy. These genetically engineered lentiviral vectors efficiently deliver genetic material encoding the CAR construct to T cells. One of the key advantages of lentiviral vectors is their ability to transduce both dividing and non-dividing cells, making them highly versatile for in vitro T cell modification. The self-inactivation (SIN) design of modern lentiviral vectors enhances safety by preventing the generation of replicating viruses and reducing the risk of insertional mutations. Furthermore, lentiviruses provide stable genome integration, ensuring long-term expression of the CAR transgene in modified T cells. The scFv(EGFR)-CD28-CD3zeta CAR construct itself contains an anti-EGFR single-chain variable region fragment (scFv) derived from a monoclonal antibody, enabling specific targeting of EGFR-expressing cancer cells. This CAR design employs a second-generation structure, incorporating CD28 and CD3ζ signaling domains, which synergistically enhances T cell activation, proliferation, and cytotoxicity compared to first-generation CARs, and improves their persistence.

This engineered lentivirus can be used to develop CAR-T cell therapies that specifically target EGFR-overexpressing malignancies. Epidermal growth factor receptor (EGFR) is frequently overexpressed or mutated in a variety of solid tumors, including glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and colorectal cancer, making it a highly attractive therapeutic target. scFv(EGFR)-CD28-CD3ζ CAR-T cells generated using this lentiviral vector can recognize and eliminate EGFR-positive tumor cells through direct cytotoxicity and cytokine release. Clinical applications are primarily focused on cancers with high EGFR expression that are resistant to conventional therapies. In glioblastoma patients, EGFR amplification occurs in approximately 40% of cases, and these CAR-T cells offer a promising approach to overcoming the blood-brain barrier limitations of antibody therapies.