TUMOR VACCINES AND BONE MARROW TRANSPLANTATION
Dana-Farber Cancer Institute, Boston MA
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Abstract
DESCRIPTION: (Applicant's Description) Bone marrow transplantation for malignant disease elicits anti-tumor activity through the combined effects of the intensive chemotherapy and radiation therapy employed for conditioning the recipient and the graft versus tumor reaction associated with the transfer of allogeneic hematopoietic cells. Unfortunately, both of these therapeutic maneuvers also induce a significant immunodeficiency in the bone marrow transplant recipient. The clinical importance of the post-transplant immunodeficiency has stimulated considerable interest in devising strategies aimed at either accelerating the time required for immunologic reconstitution or at enhancing immunologic function early post-transplant. Little attention has been devoted, however, to studying tumor vaccination in the context of bone marrow transplantation. In this application, we propose to explore the ability of new vaccination strategies to enhance anti-tumor immunity in murine model systems following bone marrow transplantation. A major goal of this investigation is to determine whether anti-tumor immunity can be augmented in this setting without the concurrent exacerbation of GVHD. The specific aims of this proposal are: 1. To characterize the biologic activity of whole tumor cell based vaccination strategies following bone marrow transplantation in murine tumor model Systems; 2. To characterize the biologic activity of tumor antigen based vaccination strategies following bone marrow transplantation in murine tumor model systems; 3. To study the potential synergistic activities of combining graft versus tumor effects with vaccination strategies following bone marrow transplantation in murine tumor model systems.
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