The AACR-The ASCO Cancer Foundation Young Investigator Translational Cancer Research Award provides funding to promising investigators to encourage and promote quality research in clinical oncology. The purpose of this award is to fund physician-scientists during the transition from a fellowship program to a faculty appointment. The award is open to physicians (M.D., D.O. or international equivalent) or physicians holding a combined M.D./Ph.D. Applicants must be working in an oncology laboratory or clinical research setting in an academic medical institution. Research projects are restricted to translational cancer research.
2010 GRANTEE
Aude Georgiana Chapuis, M.D.Senior Fellow, Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA
Targeting Melanoma with Anti-CTLA-4 and NY-ESO-1-Specific Cytotoxic T Cells
"Transfer of antigen-specific CD8+ T cells (adoptive transfer) has demonstrated a significant although transient clinical benefit in a subset of patients with metastatic melanoma. Previous studies have led to the conclusion that its effectiveness may be further improved by extending the survival of transferred T cells, and broadening the range of targeted tumor antigens. Surface expression of CTLA4 is increased on activated T cells, and when engaged to its ligand on antigen presenting cells, functions as an inhibitory receptor to dampen T cell activation. Therefore, the administration of a blocking antibody specific for CTLA4 (anti-CTLA4) has the potential to enhance T cell responses. This project proposes a combined biologic strategy involving the use of adoptively transferred NY-ESO-1-specific CD8+ T cells and concomitant administration of anti-CTLA4 in patients with metastatic melanoma. Two cohorts of 10 patients with metastatic melanoma will receive NY-ESO-1-specific T cells preceded by low-dose cytoxan to induce a suppression of regulatory T cells. The second cohort will receive the same regimen followed by administration of ipilimumab (humanized anti-CTLA4 antibody). We hypothesize that anti-CTLA4 may not only result in enhancing tumor lysis by transferred T cells, but also promote endogenous T cell responses against tumor-associated antigens released in the pro-inflammatory environment following tumor lysis (antigen spreading) and resulting in enhanced tumor response rate. Because NY-ESO-1 is strongly expressed in many tumor types but only minimally in normal tissue, this research may result in a reliable means to propagate antigen spreading and may potentially result the development of a distinct clinical tool in cancer therapy applicable to multiple tumor settings. Receiving the AACR-ASCO Cancer Foundation Young Investigator Translational Cancer Research Award is a great privilege as it provides significant support for this project and is essential to further my development as a physician-scientist in translational cancer research. With the enthusiastic support of my mentors, Drs. Philip D. Greenberg and Cassian Yee, as well as the environment of Fred Hutchinson Cancer Research Center, this award will be determinant in fostering this exciting project."
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