Our laboratory studies immunobiology and immunotherapy of human cancer, specifically, of oral carcinoma. Date Added: 8/4/2003 1:21:00 PM
Last Updated: 8/26/2003 2:21:00 PM
Description of projects available to graduate students:
Research Interest:Our laboratory studies immunobiology and immunotherapy of human cancer, specifically, of oral carcinoma. As a part of a broadly-designed research program in human head and neck cancer (HNC), we are studying immune markers (mainly those present on T, NK and DC) to evaluate their prognostic significance. The role of immune effector cells and their subsets in tumor progression is evaluated. We study ex vivo immunogenicity of tumor-derived epitopes presented on DC to immune cells and attempt to define the usefulness of these epitopes for vaccines. We also develop methods for quantitation of the frequency of vaccine-specific or tumor-specific T lymphocytes. One of the unique aspects of the program is the expertise we have developed in the evaluation of factors that contribute to poor immune responses and apoptosis of immune cells at the tumor site as well as in the peripheral circulation of patients with cancer. Signaling molecules associated with TcR in T cells and FcgRIII in NK cells, such as the z chain, are being studied as possible biomarkers of decreased lymphocyte function in cancer. Multicolor flow cytometry incorporating markers of apoptosis is being adapted to measure the proportions of T cells undergoing apoptosis at the tumor site and in the circulation of patients with cancer before and after immunotherapy. The mechanisms responsible for lymphocyte apoptosis, including the contribution of the TNF family of receptors and ligands to apoptosis of selected lymphocyte subsets in these patients are also being assessed. Effects of cytokines on T-cell apoptosis is evaluated, and cytokines best able to decrease or prevent spontaneous apoptosis of effector cells are especially targeted. Finally, expression and function of apoptosis inhibitory molecules such as FLIP and FAP-1 in tumor cells are evaluated in order to be able to decrease and eventually to abolish resistance of tumor cells to apoptosis mediated by immune cells or other apoptosis-inducing therapies. The major emphasis has been on the generation of effective cellular immune responses in patients with cancer and on protection of immune cells from tumor-induced death by the use of exogenous cytokines and other immunomodulatory agents. At the same time, we are purifying and characterizing immunogenic epitopes from human SCCHN in hope of using them as components of anti-tumor vaccines in the future.
Projects available to students:a) Initiate a clinical phase I trial of active immunization in patients with advanced oral cancer with a DNA-based semi-allogeneic vaccine (this protocol is now approved by RAC and is being re-submitted to the FDA).).b) Studies of the mechanisms responsible for spontaneous death of immune effector cells in the tumor microenvironment and circulation of patients with cancer.c) Initiate in vivo study of the rapid T-cell turnover in patients with HNC, using non-radioactive glucose for labeling of CD4+ and CD8+ T cells (a clinical protocol has been written).d) Studies of biochemical characterization of helper and cytotoxic epitopes in HNC with expectation that those shown to be immunogeneic ex vivo can then be used as synthetic epitopes for immunizations in patients with HNC.
Techniques graduate student will learn:
All immunologic techniques, including antibody assays, cell culture, cytotoxicity, ELISPOT, proliferation, flow cytometry/tetramers, apoptosis assays, Western blots, ISH, PCR, digital imaging, transfection, selection, gene arrays, microscopy.
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