Dr. Lyerly's primary interest is the development of an active immunotherapy vaccine for cancer that will generate a sufficiently strong, specific anti-tumor immune response so as to destroy any micrometastatic disease after surgical debulking of a malignant tumor. He is interested in the basic immunology and cell biology of antigen presentation to T cells in the development of anti-tumor immunity so that the development of a human cancer vaccine proceeds in a logical and methodical fashion from principles of basic science. This proposal is based upon the premise that a clinically effective cell-mediated immune response against human tumors can be elicited by activation of tumor antigen-specific CDplus cytotoxic T lymphocytes (CTL). We propose to test the hypothesis that a CD4plus T helper response of the Th1 type is necessary for effective generation of CD8plus tumor antigen specific CTL. We will test the hypothesis by analyzing peripheral blood mononuclear cells isolated from patients undergoing a phase II clinical trial of active immunotherapy with autologous dendritic cells transfected with carcinoembryonic antigen (CEA) RNA. We feel that the specific aims reflect a methodical and logical progression of studies necessary to determine the role of CD4plus T cells in eliciting a CD8plus tumor specific CTL response in cancer patients. The information resulting from this work will play an important role in designing further clinical trials of active immunotherapy using dendritic cell technology.
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| Mosca, P J; Hobeika, A C; Clay, T M et al. (2000) A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-gamma treatment. Blood 96:3499-504 |
