DuPont Guerry, MD Medline search
Professor of Medicine
Director, Hematology-Oncology Fellowship Program

515 Maloney Bldg.
Philadelphia, PA 19104

(215) 662-4137
(215) 662-4646 fax

Research Program
The Immunobiology and Immunotherapy of Melanoma

Program Summary
This segment of a broad, multidisciplinary program in melanoma and its precursors addresses the cellular host response and related natural history of human cutaneous melanoma and its precursor lesions, as well as immune-based therapies of disseminated disease. Its basic laboratory component addresses two related hypotheses.

First, biologically early melanoma provokes and partially mediates and modulates an antigen driven, MHC-restricted T cell response which is relevant to tumor progression. Biologically advanced melanoma is unseen by or suppressive of this cellular immune response.

Second, transfer and expression of genes enabling melanoma cells as antigen presenting cells will elicit T cell responses in vitro and in vivo. Used as therapeutic reagents, such cells may produce clinically meaningful tumor regressions in patients. Central to this effort is a large, well studied group of patients with melanoma and precursor pigmented lesions and patient-derived host immune cells and lesional cell lines and short term cultures.

Current studies are directed to four lines of exploration:

1) an in situ and in vitro analysis of melanoma-associated MHC antigens and co-stimulatory molecules as expressed by tumor cells of various steps in tumor progression;
2) the construction of prognostic models examining the relationship of expression of these molecules to such outcome measures as T cell infiltration of lesions and patient survival;
3) restoration of the capacity to melanoma cells to interact with immune cells by transducing them with relevant cDNAs (e.g., the costimulatory molecule, B7-1, and the multifunctional cytokine, IL-12); and,
4) evolution of clinical trials based on the:strategy of "therapeutic vaccination" with genetically engineered tumor cells.

Associated Faculty
Lynn Schuchter, M.D. (Medicine)
Stephen Eck, M.D. (Medicine, IHGT)
William Lee, M.D. (Medicine)
Meenhard Herlyn, D.V.M. (Wistar)
Linda Callans, M.D. (Surgery)