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.In the previous annual report, SBVPF had 6 clinical reagents in development: 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.We successfully completed the manufacturing (MCB and vector) for EGFRvIII CAR, SS1 CAR and ECCE. The TYR-450 TCR was put on production hold. The MAGE-A12 and A3 (A1-restricted) have been completed. In addition, we manufacture a CAR targeting mesothelin, which is now being used in a clinical trial.We currently have two murine NY-ESO-1 TCR, two chondroitin sulfate proteoglycan CARS, thyroglobulin TCR, a DP4-retricted anti-MAGE-A3 TCR and an iCaspase9 suicide vector in production.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. We are also generating 13 adenoviral vector constructs.In addition to our reagent development and production efforts, my laboratory is also involved in basic research to identify novel targets for immunotherapy. We are 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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