HUMAN MINOR HISTOCOMPATIBILITY ANTIGENS - NEW CONCEPTS FOR MARROW TRANSPLANTATION AND ADOPTIVE IMMUNOTHERAPY

Bone marrow transplantation (BMT) is the present treatment for hematol ogical malignancies. Two major drawbacks of allogeneic BMT are graft-v ersus-host disease (GVHD) and leukemia relapse. The use of HLA-matched siblings as marrow donors results in the best transplant outcome. Non etheless, the results of clinical BMT reveal that the selection of MHC -identical donors' bone marrow (BM) is no guarantee for avoiding GVHD or ensuring disease-free survival even when donor and recipient are cl osely related. It is believed that non-MHC-encoded so-called minor his tocompatibility antigens (mHag) are involved in both graft-versus-host and graft-versus-leukemia activities. The recent new insights into th e chemical nature of mHag not only reveal their physiological function but, more importantly, provide insights into their role in BMT. Toget her with the information on the human mHag genetics and tissue distrib ution gathered in the past, we may now apply this knowledge to the ben efit of human BMT. Directly relevant is the utility of mHag molecular typing for diagnostics in BM donor selection. Most promising is the us e of mHag-specific cytotoxic T cells for adoptive immunotherapy of leu kemia.