The """"""""Genetic Approaches to Cancer Immunotherapy"""""""" Program is a translational research program dedicated to the conceptualization, development and clinical evaluation of novel immunotherapies that are based on gene transfer and somatic cell engineering. This innovative and highly interactive program brings together investigators with expertise in tumor immunology, transplantation biology, gene transfer biology and noninvasive imaging technologies, who share the common goal of exploring the potential advantages of genetic strategies to treat cancer. Gene transfer into patient cells, transplant donor cells, or engineered auxiliary cells such as antigen-presenting cells, is integral to all projects and supported by the Gene Transfer Core. Multimodality imaging, to study the migration, persistence and activation status of genetically modified cells in vivo, is also preeminent and supported by the Imaging Core. The 3 projects and 3 cores are: 1. Artificial antigen presentation to sensitize virus-specific T cells for adoptive immunotherapy;2. Genetic approaches to immune adjuvants;3. Genetic approaches to enhance the anti-tumor functions of T Lymphocytes;Gene Transfer and Somatic Cell Engineering Core;Imaging Core;Administrative Core. This program integrates scientific discovery, preclinical development, vector production, and patient cell transduction, within a single institution's continuum. This program is the foundation for preclinical and clinical research in genetic medicine and somatic cell engineering at MSKCC. The present revised application is a competitive renewal to continue this research and apply it in the clinical setting. We propose 5 clinical trials that make use of either retroviral-mediated gene transfer or plasmid DNA to genetically modify T lymphocytes or antigen-presenting cells, all of which aim to enhance specific immunity in cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA059350-17
Application #
7825461
Study Section
Subcommittee G - Education (NCI)
Program Officer
Merritt, William D
Project Start
1998-05-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
17
Fiscal Year
2010
Total Cost
$2,081,408
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Yeku, Oladapo; Li, Xinghuo; Brentjens, Renier J (2017) Adoptive T-Cell Therapy for Solid Tumors. Am Soc Clin Oncol Educ Book 37:193-204
Daniyan, Anthony F; Brentjens, Renier J (2017) Immunotherapy: Hiding in plain sight: immune escape in the era of targeted T-cell-based immunotherapies. Nat Rev Clin Oncol 14:333-334
Sadelain, Michel; Rivière, Isabelle; Riddell, Stanley (2017) Therapeutic T cell engineering. Nature 545:423-431
Yeku, Oladapo O; Brentjens, Renier J (2016) Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy. Biochem Soc Trans 44:412-8
Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J et al. (2016) Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol 13:25-40
Jackson, Hollie J; Rafiq, Sarwish; Brentjens, Renier J (2016) Driving CAR T-cells forward. Nat Rev Clin Oncol 13:370-83
Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13
Daniyan, Anthony F O; Brentjens, Renier J (2016) At the Bench: Chimeric antigen receptor (CAR) T cell therapy for the treatment of B cell malignancies. J Leukoc Biol 100:1255-1264
Hasan, A N; Selvakumar, A; Shabrova, E et al. (2016) Soluble and membrane-bound interleukin (IL)-15 R?/IL-15 complexes mediate proliferation of high-avidity central memory CD8(+) T cells for adoptive immunotherapy of cancer and infections. Clin Exp Immunol 186:249-265
Khalil, Danny N; Smith, Eric L; Brentjens, Renier J et al. (2016) The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 13:273-90

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