Minor histocompatibility antigens in cancer therapy after allo-SCT

In allo-SCT, an immune reaction between donor T cells and recipient histocompatibility antigens (mHags) can give rise to very potent graft-versus-tumour (GVT) effects. The effectiveness of donor lymphocyte infusions in the treatment of leukaemia relies on this principle. However, there is also an inherent danger in allo-SCT because immune reactions between donor and recipient cells can cause significant adverse effects ranging from graft rejection by the recipient to graft-versus-host-disease (GVHD). Matching for HLA molecules between donor and recipient lowers the risk for GVHD but is unable to eliminate it. HLA-identical allo-SCT is still followed by GVHD in 20-50% of the cases. In this scenario, donor T cells are not directed against HLA-peptide complexes but against minor histocompatibility antigens (mHags) displayed on HLA molecules. The immune response of donor T cells against recipient mHags is thought to be the key in the GVT effect seen in allo-SCT. Since their discovery, mHags have become a focus of research because they carry the potential for separating the beneficial GVT effect from deleterious GVHD