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Degree

Doctor of Philosophy, Ohio State University, Medical Science, 2006.

Abstract

Years of clinical and experimental evidence have shown that both the antigen-nonspecific innate immune system and the antigen-specific adaptive immune system can effectively eliminate malignant cells that remain after front-line therapy for cancer. Because the immune response to any given stimulus requires the coordinated activity of a large number of diverse cell types, elaborate communication networks have evolved that utilize direct cell-cell interactions as well as soluble growth factors, or cytokines, that can potentially travel great distances in the body. Knowledge of the mechanisms and effects of these cell-cell and cell-cytokine-cell interactions is of paramount importance as physicians and scientists advance the frontiers of cancer immunotherapy. Presented here is a series of studies that define roles for the cytokine interleukin 15 (IL-15) in acute graft versus host disease (GVHD) and graft rejection. Mediated by both the innate and adaptive immune systems, graft rejection and acute GVHD are the most common life threatening side effects of allogeneic bone marrow transplantation (BMT), a promising immunotherapeutic approach for aggressive and otherwise incurable hematopoietic malignancies. Also presented are studies evaluating a novel therapeutic antibody designed to interrupt the cell-cell signals that serve to prevent tumor cell lysis by natural killer (NK) cells, a critical part of the innate immune system. Together, these data unravel a small portion of the complex interactions between immune effector cells and malignant cells and provide justification for future basic and clinical immunotherapeutic studies.

Keywords

IL-15; bone marrow transplantation; graft versus host disease; T cell; NK cell

Advisor

Michael A Caligiuri

Pages

168p.

Document number: osu1145978587
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=osu1145978587

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