Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy

Authors


  • I would like to thank Els Blokland and Jos Pool for their contributions over the years to the original work of the laboratory. I am indebted to: Marleen de Bueger, Cécile van Els, Joke den Haan, Dick van der Harst, Linda Liem and Ellen van Lochem for their essential scientific contributions: Isabelle Miconnet. Tuna Mutis and Ellen Schrama for fruitful discussions, and Roel Willemze. Fred Falkenburg and Jaak Vossen whose patients were included in the investigations. I am grateful to Jon van Rood, who performed the last minute critical reading, and Ingrid Curiel for the superb typing. I thank Drs. Roosnek, Simmons and Taurog for providing the results of their work before publication. This work was supported in part by grants from the Dutch Organisation for Scientific Research (NWO), the Dutch Cancer foundation, the J, A, Cohen Institute for Radiopathology Radiation Protection (IRS), and the Macropa Foundation, as well as a European Biotech EC grant.

Abstract

Summary: Bone marrow transplantation (BMT) is the present treatment for hematological malignancies, Two major drawbacks of allogeneic BMT are graft-versus-host disease (GVHD) and leukemia relapse. The use of HLA-matched siblings as marrow donors results in the best transplant outcome. Nonetheless, 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 closely related. It is believed that non-MHC-encoded so-called minor histocompatibility antigens (mHag) are involved in both graft-versus-host and graft-versus-leukemia activities. The recent new insights into the chemical nature of mHag not only reveal their physiological function but, more importantly, provide insights into their rule in BMT. Together with the information on the human mHag genetics and tissue distribution gathered in the past, we may now apply this knowledge to the benefit of human BMT. Directly relevant is the utility of mHag molecular typing for diagnostics in BM donor selection. Most promising is the use of mHag-specific cytotoxic T cells for adoptive immunotherapy of leukemia.

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