EFFICACY OF CD28 ANTIBODY FOR GVHD PREVENTION

University Of Washington, Seattle WA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies showed that administration of an agonistic CD28 antibody could prevent GVHD in mice. In studies to date, we found that administration of a CD28 antibody was not sufficient by itself to prevent severe acute GVHD after MHC-haploidentical HCT in a baboon. Subsequent studies were delayed by difficulty in obtaining appropriate donor-recipient pairs. Two additional baboons have been treated with the CD28 antibody in combination with methotrexate and tacrolimus. Both recipients had prompt autologous hematopoietic recovery without GVHD. Autologous hematopoietic recovery was most likely explained by sub-myeloablative irradiation of the spine and pelvic bones related to inadvertent unidirectional exposure to the linear accelerator during total body irradiation (TBI).