Jingyu Zhao, MS
Direct In Vivo Engineering of CAR-T Cells for Cost-Effective Cancer Therapy
Abstract
Chimeric Antigen Receptor T cell (CAR-T) therapy is highly effective against B cell lymphoma but is limited by complex, costly production processes. We propose an innovative in vivo CAR-T approach using an advanced lentiviral system to generate CAR-T cells directly in the patient. Our method employs a Nipah virus (NiV) pseudotyping strategy, with mutations in receptor-binding sites and an anti-CD3 scFv for targeted T-cell delivery. Enhanced by transduction enhancers (TE) Vectofusin-1 and Poloxamer 407, the NiV+TE combination has shown superior T-cell transduction and effective tumor elimination in preclinical models. We will evaluate this system against B cell lymphoma (CD19-CAR) and solid tumors (B7H3-CAR) in xenograft and syngeneic models, assessing efficacy, off-target effects, and toxicity. This approach could overcome current CAR-T limitations, offering a more accessible, cost-effective therapy.
I am deeply honored to receive the PhRMA Foundation Fellowship and to connect with peers and experts in this community. This will further inspire me to advance my research on a cost-effective and efficient gene-engineering strategy for cancer immunotherapy, ultimately benefiting more patients.
