CANDIDATE: As a medical oncologist aiming to become an innovative and productive independent clinical investigator, I plan to use this award period to acquire the training and experience necessary to translate discoveries of immunology research into clinical cancer immunotherapies. ENVIRONMENT AND MENTOR: The NYU Cancer Institute offers a fertile environment for physician- scientists committed to translational research. Protected time allows an 80% dedication to the research proposed. Our Tumor Vaccine Program is focused on the development of more potent cancer vaccines and vaccine adjuvants, and provides critical infrastructure to support my proposed work. My mentor, Dr Nina Bhardwaj, is a world expert on dendritic cells (DCs), nature's most potent antigen presenting cells, and is particularly interested in the use of DCs as vaccine adjuvants in human subjects. RESEARCH PROJECT: The research objective is to demonstrate the role of CpG 7909, a Toll-like receptor (TLR) 9 ligand, as a vaccine adjuvant in the treatment of cancer. Cancer vaccines are an ideal treatment modality, since they are highly selective and induced immunity can lead to tumor regressions and the prospect of conferring life-long protection. TLRs control multiple DC functions and adaptive immune responses in addition to their role in innate immunity. TLR ligation represents a novel approach to augmenting cancer vaccines. We propose to conduct a Phase I cancer vaccine trial composed of the combination of the TLR 9 agonist CpG 7909, Montanide (a commonly used vaccine adjuvant) and NY-ESO- 1 protein (a highly immunogenic cancer antigen expressed by a variety of solid tumors). After establishing the safety, feasibility and immunogenicity of this novel combination, we plan to perform an additional randomized trial comparing NY-ESO-1 protein emulsified in Montanide alone to the same emulsion with the co-administration of CpG to evaluate if the addition of CpG adjuvant is a superior approach. While based on very promising data from animal studies, it constitutes the first trial in humans using the combination of CpG and Montanide for a protein vaccine. The use of the full length recombinant NY-ESO-1 protein allows for inclusion of patients of all HLA-types and is expected to generate a strong broad adaptive immune response, including T helper 1, CD8+ T cells and B cells.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Lim, Susan E
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Fiscal Year
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New York University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Adams, Sylvia; Kozhaya, Lina; Martiniuk, Frank et al. (2012) Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin Cancer Res 18:6748-57
Kwon, Simona; Rideout, Catlin; Tseng, Winston et al. (2012) Developing the community empowered research training program: building research capacity for community-initiated and community-driven research. Prog Community Health Partnersh 6:43-52
Dewan, M Zahidunnabi; Vanpouille-Box, Claire; Kawashima, Noriko et al. (2012) Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer. Clin Cancer Res 18:6668-78
Ott, Patrick A; Adams, Sylvia (2011) Small-molecule protein kinase inhibitors and their effects on the immune system: implications for cancer treatment. Immunotherapy 3:213-27
Adams, Sylvia; Greeder, Luba; Reich, Elsa et al. (2011) Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention? Cancer Immunol Immunother 60:999-1007
Yuan, Jianda; Ginsberg, Brian; Page, David et al. (2011) CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases. Cancer Immunol Immunother 60:1137-46
Kris, Mark G; Benowitz, Steven I; Adams, Sylvia et al. (2010) Clinical cancer advances 2010: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol 28:5327-47
Adams, Sylvia; Chakravarthy, A Bapsi; Donach, Martin et al. (2010) Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival. Breast Cancer Res Treat 124:723-32
Bogunovic, Dusan; O'Neill, David W; Belitskaya-Levy, Ilana et al. (2009) Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proc Natl Acad Sci U S A 106:20429-34
Adams, Sylvia (2009) Toll-like receptor agonists in cancer therapy. Immunotherapy 1:949-64

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