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 nave T cells to make them specifically recognize and kill tumor. To that end, SBVPF has developed and produced nine master cell banks and seven retroviral vectors: mF5 TCR, recognizing melanoma antigen recognized by T cells antigen (MART-1);CEA TCR, recognizing carcinoembryonic antigen;2G1 TCR, recognizing a renal cell carcinoma antigen;CD19 CAR, recognizing CD19 for the treatment of a variety of B cell malignancies;VEGF-R2 CAR, recognizing VEGF-R2 on tumor vasculature;hIL-12, a vector encoding the cytokine, IL-12, to augment T cell function;MAGE-A3 TCR, targeting the MAGE-A3 cancer testis antigen;DMF5 TCR, a human TCR targeting MART-1. In addition, we currently have our first lentiviral vector under development which is a TCR directed against MART-1. Of note, a standard retroviral or lentiviral vector production run provides enough viral vector to treat approximately 150 patients with cancer. The retroviral vector production can be easily scaled up to double the number of patient treatments to nearly 300. Efforts are currently underway in my laboratory to develop a CAR directed against Mesothelin for the treatment of mesothelin-positive cancers such as mesothelioma or pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC010989-03
Application #
8158347
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2010
Total Cost
$532,491
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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