Targeting of Human Dendritic Cells for Melanoma Therapy

Baylor Research Institute, Dallas TX

Investigators

Abstract

DESCRIPTION (provided by applicant): Dendritic cells (DCs) express diverse surface proteins known, or suspected, to be involved in antigen capture. Included among these are C-type lectin receptors (CLRs). DCs themselves have different subtypes/activation states that direct diverse responses to antigens. The central hypothesis of this project is that vaccines based on melanoma antigen-conjugates targeted specifically to distinct human DCs will elicit potent T lymphocyte responses leading to tumor destruction. Dr. Prilliman will investigate optimal antigen delivery to DC via generating monoclonal antibodies (MAbs) to those CLRs most likely to be involved in antigen capture (e.g., DEC-205 and DC-SIGN). She will use the MAbs as surrogate ligands to direct the human melanoma antigen MART-1/Melan-A to specific DC types and examine anti-tumor CD4* and CDS* T cell responses in vitro and in vivo. Targeting different receptors, even on the same DC, may effect the rate of antigen uptake and subsequent processing and presentation of specific MART-1/Melan-A peptide epitopes for T-cell priming. Also, engaging some CLRs can lead to specific activation events that influence the outcome of the induced T cell responses. The studies proposed herein will lead to identification of those DC-expressed targets able to prime the strongest MART-1/Melan-A-specific CDS* CTL responses. The immediate goal of the candidate is to procure training in the areas of human tumor and DC biology to enhance her research skills and allow her to develop a career as an independent investigator in translational human cancer research. This will be accomplished through a coursework and research program under the Sponsorship of Drs. Jacques Banchereau and Karolina Palucka at the Baylor Institute for Immunology Research (BUR). Drs. Gerard Zurawski (BUR) and Ralph Steinman (Rockefeller University) will also serve on the Advisory Committee. Both the BUR and the laboratory of Dr. Steinman are committed to studying DC biology and its relevance to human diseases, including cancer.