Targeting haematopoietic-specific minor histocompatibility antigens to distinguish graft-versus-tumour effects from graft-versus-host disease

Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions can induce durable remission in patients with haematological malignancies through a graft-versus-tumour (GvT) effect. In human leukocyte antigen (HLA)-matched settings, this powerful immunotherapeutic effect is predominantly mediated by donor T cells directed at the recipient's minor histocompatibility antigens (mHags) presented on malignant cells. The mHags are short peptides excised from polymorphic regions of intracellular proteins, and are presented by HLA molecules to donor T cells. Several ubiquitously expressed mHags are involved not only in GvT but also in graft-versus-host disease (GvHD). However, a specific set of mHags is expressed exclusively by haematopoietic cells and their malignant counterparts. Targeting these haematopoietic mHags is an attractive strategy to induce specific GvT effects without increasing the risk of GvHD. This chapter will summarize the current efforts to identify therapeutically relevant haematopoietic mHags, and outline the strategies to apply mHag-based cellular immunotherapy to treat recurrent malignancies after allo-SCT.