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. In the previous annual report, SBVPF had developed and produced nine master cell banks and seven retroviral vectors: mF5 TCR, CEA TCR, Trail-DR4 TCR, CD19 CAR, VEGF-R2 CAR, hIL-12, MAGE-A3 TCR, DMF5 TCR. We now report the development and/or manufacture of an additional 6 master cell banks and retroviral vector supernatants: EGFRvIII CAR, targeting the epidermal growth factor variant III on gliomas;TYR-450 (DR4 Class II-restricted) TCR, targeting Tyrosinase;SS1 CAR, targeting mesothelin;MAGE-A12 (Cw7-restricted) TCR, targeting the MAGE cancer testis antigen;MAGE-a3 (A1-restricted) TCR, targeting the MAGE cancer testis antigen;and an artificial antigen presenting cells (ECCE), for replacement of pheresis-derived feeder cells in our expansion process. In addition, we have manufactured our first lentiviral vector which is a TCR directed against MART-1. A clinical protocol utilizing this vector is currently under development. Our laboratory has also provided cloning services to our group. We have constructed 12 lentiviral vectors using gateway technology for cell reprogramming. We have also developed new clinical retroviral and lentiviral vector backbones to facilitate our clinical reagent program. In addition to our reagent development and production efforts, my laboratory is also involved in basic research to identify novel targets for immunotherapy. As mentioned, we developed a chimeric antigen receptor, SS1, targeting mesothelin for which a clinical protocol is being prepared. Our expectation is that the clinical trial will initiate in the Fall of 2011. We are also exploring two additional targets which involves expression screening, TCR cloning and functional analyses to assess whether these new targets are viable options for adoptive cell transfer studies.
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