Identifying stop codon-generated minor histocompatibility antigens capable of eliciting potent GVL or GVHD alloresponses
Minor histocompatibility antigens (mHAgs) are molecules on the surface of cells that differ between donor and recipient during allogeneic hematopoietic cell transplantation (HCT), and can elicit either a potentially curative graft-versus-leukemia (GVL) effect or life-threatening graft-versus-host disease (GVHD). Effectively separating GVL from GVHD is a major goal in curing hematologic malignancies with HCT. With the financial support of a grant from Gabrielle’s Angel Foundation for Cancer Research, the goal of Dr. Brickner’s team is to identify and characterize mHAgs which differ dramatically between donor and recipient due to normal genetic variations in the length of proteins, and to assess the impact of these so-called “stop codon-generated” mHAgs on GVL and GVHD. These studies will help lead to a better understanding of mHAgs, and will hopefully identify of a number of new clinically relevant mHAgs that can be therapeutically targeted to enhance GVL effects while reducing GVHD in HCT patients.