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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC010989-05
Application #
8554091
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$475,840
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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:
Abate-Daga, Daniel; Lagisetty, Kiran H; Tran, Eric et al. (2014) A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther 25:1003-12
Rosati, Shannon F; Parkhurst, Maria R; Hong, Young et al. (2014) A novel murine T-cell receptor targeting NY-ESO-1. J Immunother 37:135-46
Feldman, Steven A; Xu, Hui; Black, Mary A et al. (2014) Use of the piggyBac transposon to create stable packaging cell lines for the production of clinical-grade self-inactivating ?-retroviral vectors. Hum Gene Ther Methods 25:253-60
Casati, Anna; Varghaei-Nahvi, Azam; Feldman, Steven Alexander et al. (2013) Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients. Cancer Immunol Immunother 62:1563-73
Morgan, Richard A; Chinnasamy, Nachimuthu; Abate-Daga, Daniel et al. (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36:133-51
Zhang, Ling; Feldman, Steven A; Zheng, Zhili et al. (2012) Evaluation of ?-retroviral vectors that mediate the inducible expression of IL-12 for clinical application. J Immunother 35:430-9
Bear, Adham S; Morgan, Richard A; Cornetta, Kenneth et al. (2012) Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther 20:246-9
Morgan, Richard A; Johnson, Laura A; Davis, Jeremy L et al. (2012) Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum Gene Ther 23:1043-53
Yang, Shicheng; Karne, Neel K; Goff, Stephanie L et al. (2012) A simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes. Hum Gene Ther Methods 23:73-83

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