Graft rejection is a major problem in bone marrow transplantation for hematologic malignancies. This proposal is based on the observation that the treatment of canine bone marrow recipients with monoclonal antibody S5 from day -7 to day -2 before total body irradiation and transplantation facilitates engraftment of DLA-mismatched marrow. Preliminary data suggest that S5 recognizes a 90kD glycoprotein that may have functional analogy with lymphocyte homing receptors. These human gp90s have been implicated in the adhesion of lymphocytes to high endothelial venules (HEV). For this reason, we have hypothesized that the pretreatment with S5 antibody impairs the host lymphocytes, ability to mediate an immune response against the incoming marrow. The goals of the proposed study include: 1. To more precisely determine the distribution of S5 on functionally distinct bone marrow populations, lymph nodes, and other tissues in the reticuloendothelial system. This will be done on specimens labeled in vitro and on tissue retrieved after in vivo injection. 2. To test the effects of S5 on immune function by: 1) adding the antibody to in vitro assays of lymphocyte function, 2) evaluating the function of cells retrieved from animals after in vivo injection, and 3) testing the effect of S5 on in vivo immune function. 3. To do further structural characterization of the canine gp90 by biochemical and molecular genetic analysis. The candidate is committed to the establishment of a career in academic medicine as a laboratory-based investigator. Fred Hutchinson Cancer Research Center has a unique blend of investigators in both the Clinical and Basic Sciences Divisions with expertise in all aspects of the proposed project along with having the facilities and necessary equipment for the accomplishment of the proposed research. The University of Washington is available for courses pertaining to the field of the proposed field of study.
