Timothy J. Eberlein, M.D.

DEPARTMENT OF Surgery
Peter S. Goedegebuure, Ph.D.
Keywords: breast carcinoma, dendritic cells, pancreas carcinoma, T lymphocytes, vaccine, T reg

Over the past several years, our laboratory has focused on the T cell response to breast carcinoma with the goal to design a vaccine for treatment. As a part of this process, two breast cancer-associated molecules, Her2/neu and mammaglobin were investigated for their ability to induce T cell responses. We identified several CD8 T cell epitopes in both tumor antigens, suggesting both proteins could potentially be tumor rejection antigens. Our current studies focus on the design of Her2/neu and mammaglobin-based vaccines that induce antitumor immune responses in vivo. We recently developed a novel system for the introduction of proteins or protein fragments into professional antigen-presenting cells, particularly dendritic cells. The dendritic cells process Her2/neu or mammaglobin protein and present MHC-bound peptides to T cells. Our novel delivery system has shown encouraging results for both Her2/neu and mammaglobin. Our next step will be to test the novel delivery system in vivo for which we will use a transplantable tumor model, a neu transgenic mouse model, and possibly a xenograft model in which both breast and pancreatic tumors will be treated with in vitro-stimulated T cells.

In addition to vaccination, we have started to investigate mechanisms of immuosuppression. In collaboration with Dr. David Linehan, we recently found that a particular subset of CD4⁺ T cells, regulatory T cells (T reg), is more prevalent in patients with breast or pancreatic cancer than in normal controls, and in mice the prevalence of T reg increases with tumor progresion. Purified T reg were found to suppress proliferation and cytokine secretion of non-T reg, and as such T reg may inhibit antitumor immune responses. We therefore plan to study T reg in more detail, in vitro as well as in some of the in vivo models outlined above.