Leukemia-associated antigens and minor histocompatibility antigens (LAAs and MiHAs)

Leukemia-associated antigens (LAAs) and minor histocompatibility antigens (MiHAs) are peptides presented by Human Leukocyte Antigen (HLA) molecules on the surface of hematologic malignancy cells, serving as critical targets for immunotherapy [1]. LAAs, such as WT1 and PRAME, are proteins overexpressed in leukemic cells, while MiHAs are polymorphic peptides resulting from genetic differences between a stem cell donor and the recipient [2]. These antigens are the primary drivers of the graft-versus-leukemia (GVL) effect, where donor T cells recognize and destroy residual cancer cells after allogeneic hematopoietic stem cell transplantation [3]. Therapeutic approaches include peptide vaccines like Galinpepimut-S and T-cell receptor (TCR) engineered therapies like IMA203, which aim to enhance the immune response against these specific targets [4]. A significant therapeutic challenge is the risk of graft-versus-host disease (GVHD), which occurs if the targeted antigens are also expressed on healthy non-hematopoietic tissues [5]. Additionally, malignant cells may escape immune detection through antigen loss or the downregulation of HLA presenting molecules [2]. Clinical development focuses on identifying antigens with restricted expression to hematopoietic lineages to maximize the GVL effect while minimizing systemic toxicity [1]. Sources: [1] NIH (PMC3429254), [2] NIH (PubMed 20466853), [3] NIH (PubMed 15498713), [4] NCI (Cancer Drug Information), [5] NIH (PMC6103001).

Other names

Tumor-associated antigens (TAAs)Minor histocompatibility antigens (mHAs)Leukemia-specific antigensPeptide-MHC complexes (pMHC)Graft-versus-leukemia antigens

Induction of cytotoxic T lymphocyte (CTL) response and T-cell mediated lysis of malignant cells via recognition of specific peptide-HLA complexes presented on the cell surface.