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 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 be cloned. In these instances we can use a gene therapy approach to treat patients by introducing neoantigen-specific TCRs into autologous PBMC, 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. A major focus of my laboratory in FY19 was on the commissioning and qualification of a new GMP facility for vector production with expectation to begin GMP production of retroviral vectors encoding TCRs that target individualized tumor specific mutations in FY20.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Scientific Cores Intramural Research (ZIC)
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National Cancer Institute Division of Basic Sciences
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Sabbatino, Francesco; Wang, Yangyang; Scognamiglio, Giosuè et al. (2016) Antitumor Activity of BRAF Inhibitor and IFN? Combination in BRAF-Mutant Melanoma. J Natl Cancer Inst 108:
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