Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives.
Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusion are effective treatment modalities for various hematological malignancies. Their therapeutic effect, the graft-versus-tumor (GvT) effect, is based mainly on an alloimmune response of donor T cells directed at tumor cells, in which differences in the expression of minor histocompatibility Ags (mHags) on the cells of the patient and donor have a crucial role. However, these differences are also responsible for induction of sometimes detrimental GvHD. As relapse and development of GvHD pose major threats for a large proportion of allotransplanted patients, additional therapeutic strategies are required. To augment the GvT response without increasing the risk of GvHD, specific mHag-directed immunotherapeutic strategies have been developed. Over the past years, much effort has been put into the identification of therapeutically relevant mHags to enable these strategies for a substantial proportion of patients. Currently, the concept of mHag-directed immunotherapy is tested in clinical trials on feasibility, safety and efficacy. In this review, we will summarize the recent developments in mHag identification and the clinical data on mHag-specific immune responses and mHag-directed therapies in patients with hematological malignancies. Finally, we will outline the current challenges and future prospectives in the field.
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
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Oostvogels
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
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Lokhorst
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
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D064591:Allografts; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D033581:Stem Cell Transplantation; D057170:Translational Research, Biomedical / Q000379:methods*
D006680:HLA Antigens