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

Lentiviral vectors offer several significant advantages, making them the gold standard for chimeric antigen receptor (CAR) therapy development. First, these lentiviral particles possess exceptional transduction capabilities, simultaneously transducing both dividing and non-dividing cells, crucial for treating primary human T cells that may be in different activation states. Unlike non-viral methods, lentiviral systems ensure stable integration of the CAR transgene into the host cell genome. This genomic integration guarantees sustained expression of the EGFR-specific CAR during rapid T cell proliferation and its inheritance to all progeny cells, providing durable therapeutic effects. Furthermore, the use of third-generation lentiviral packaging systems (typically pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G)) enables high viral titers and broad tropism. This combination of high transduction efficiency, stable expression, and enhanced safety makes lentiviral vectors ideal for delivering complex multi-domain CAR constructs.

The primary application of the scFv(EGFR)-CD28-41BB-CD3zeta CAR-T lentivirus is in cancer immunotherapy, particularly for solid tumors that overexpress epidermal growth factor receptor (EGFR). EGFR is a known oncogene driver gene in various malignancies, including glioblastoma, non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer. The third-generation CAR structure delivered by this virus is uniquely engineered to maximize T cell potency and lifespan. By integrating the CD28 and 4-1BB (CD137) co-stimulatory domains with the CD3ζ signaling chain, the resulting CAR-T cells utilize dual signaling pathways. The CD28 domain promotes rapid cell activation and efficient expansion, while the 4-1BB domain enhances metabolic adaptability and promotes the formation of long-lived memory T cells, which is crucial for preventing tumor recurrence. This synergistic strategy aims to overcome the harmful and immunosuppressive microenvironment of solid tumors.