Minor histocompatibility antigens as targets for T-cell immunotherapy

Abstract

Introduction. Minor histocompatibility antigens (MiHAs) — polymorphic peptides presented in HLA molecules that are products of genes containing nonsynonymous single nucleotide polymorphisms. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the immune response directed to MiHA can result both in graft-versus-host and graft-versus-tumor responses.Some MiHAs are promising and safe targets for T-cell immunotherapy of leukemia relapse after allo-HSCT.Aim — to analyze the literature describing the immune response to various MiHAs, as well as clinical trials using MiHAs as targets of immunotherapy.Main findings. MiHAs represent promising targets for the prevention or therapy of leukemia relapse after allo-HSCT due to their advantages over tumor-associated antigens and neoantigens. To be suitable for immunotherapy, MiHA must satisfy several parameters: 1) be presented by a common HLA allele, 2) have an optimal frequency of polymorphism-encoding allele, 3) be encoded by a gene that is predominantly expressed in hematopoietic tissue. This drastically limits the number of applicable targets and makes the discovery of new MiHAs highly relevant.