Minor histocompatibility antigen 2 (HA-2) (HA-2)

Minor histocompatibility antigen 2 (HA-2) is a peptide derived from the MYO1G gene (encoding Myosin IG) that is presented on the cell surface by the HLA-A*02:01 molecule. It is classified as a 'blood-restricted antigen' because its expression is predominantly limited to hematopoietic lineage cells, including various types of leukemia and normal blood cells, while being absent from non-hematopoietic tissues such as the skin, liver, and gut [9, 16]. This restricted expression profile makes HA-2 an ideal therapeutic target for T-cell receptor (TCR) based immunotherapies in the context of allogeneic hematopoietic stem cell transplantation (alloHSCT). By targeting HA-2, engineered T-cells can selectively eliminate residual leukemia cells (Graft-versus-Leukemia effect) without attacking the patient's healthy non-hematopoietic organs, thereby significantly reducing the risk of Graft-versus-Host Disease (GvHD) [6, 8]. Clinical programs such as TScan Therapeutics' TSC-101 and BlueSphere Bio's TCX-101 are currently evaluating TCR-T therapies directed against HA-2 to improve outcomes for patients with high-risk hematological malignancies [13, 17].

Other names

MYO1GMyosin IGBlood-restricted antigen 2Minor histocompatibility protein HA-2

T-cell receptor (TCR) engineered T-cells recognize the HA-2 peptide (YIGEVLVSV) presented by HLA-A*02:01 on the surface of hematopoietic cells, including leukemia cells, leading to targeted cell lysis and a graft-versus-leukemia (GvL) effect [6, 16].