Clinical production of viral vectors for cancer gene therapy

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The Surgery Branch Vector Production Facility (SBVPF) was established to provide clinical-grade retroviral and lentiviral vectors to support of our gene therapy clinical trials with the goal of providing GMP quality products while reducing production time and cost. These products, both retroviral and lentiviral vectors will be used to introduce novel T cell receptors (TCR) or chimeric antigen receptors (CAR) to genetically modify naive T cells to make them specifically recognize and kill tumor. This lab provides all the clinical viral reagents for our clinical gene therapy program. Our current focus is to isolate T cell receptors targeting nonsynonymous mutations presented by tumors from tumor infiltrating lymphocytes residing within the given tumor and testing the hypothesis that immunogenic mutations (neoantigens) presented on a patient's tumor mediate tumor regression by TIL. In some cases, TIL cannot be generated, but TCRs can still be cloned. We use a gene therapy approach to treat patients by introducing neoantigen-specific TCRs into autologous PBMC using these viral vectors, expanding the transduced cells ex vivo and administering to the patient. We have developed a small scale transient vector production platforms, gammaretroviral that support GMP-compliant transient vector production for single individualized patient treatments targeting neoantigens. Since the opening of dedicated GMP space in October 2019, the SB GMP VPF has produced 30 novel, individual vectors encoding patient specific TCRs meeting the specifications required for clinical use.