Identification of therapeutically relevant mHags and strategies for mHag‐based immunotherapy after allogeneic HSCT: where do we stand?

Abstract

Minor histocompatibility antigens (mHags) play a major role in graft‐versus‐host disease (GvHD) and graft‐versus‐leukaemia (GvL) effect following human leucocyte antigen (HLA)‐matched hematopoietic stem cell transplantation (HSCT). These antigens are defined as immunogenic peptides derived from polymorphic proteins and can be recognized by allogeneic cytotoxic T cells (CTLs) in the context of HLA molecules. The tissue distribution of mHags and HLA molecules influences the clinical outcome of T‐cell responses to these antigens. Differential T‐cell recognition of mHags specifically expressed in hematopoietic cells, including malignant cells from the recipient, may result in a beneficial GvL effect without detrimental GvHD. Furthermore, T‐cell responses against proteins solely expressed in hematopoietic cell lineages from which the malignancy is derived may be appropriate mediators of GvL reactivity without GvHD induction. mHags with hematopoiesis‐restricted expression may therefore serve as primary targets of the T‐cell‐mediated GvL/graft‐versus‐tumour (GvT) effect following HLA‐identical HSCT. This paper reviews the recent findings on methods for identification of mHags specifically functioning as GvL/GvT targets and outlines perspectives for the development of novel strategies for mHag‐based immunotherapy.