Quantification of the HA-1 gene product at the RNA level; relevance for immunotherapy of hematological malignancies.
Minor histocompatibility antigens can induce cytotoxic T cells that play an important role in the graft-versus-leukemia and graft-versus-host-disease (GvHD) activity after stem cell transplantation. Minor histocompatibility antigens (mHags) with expression limited to the hematopoietic system may have a prominent role in the graft-versus-leukemia reaction. Earlier in vitro studies demonstrated that cytotoxic T cells specific for the minor histocompatibility antigen HA-1 only lysed cells of hematopoietic origin. Despite this limited expression, an HA-1 mismatch is associated with GvHD. Yet, the hematopoietic-restricted HA-1 membrane expression motivated us to develop an ex vivo HA-1-specific protocol for cellular immunotherapy of relapsed leukemia. To ensure the feasibility and safety of such cellular therapy, broad HA-1 RNA analysis is indispensable. Here we demonstrate the hematopoietic-restricted expression at the HA-1 gene transcriptional level with high RNA expression in normal and in malignant hematopoietic cells and background expression levels in nonhematopoietic cells. In tissues that showed low HA-1 RNA expression, hematopoietic cells were present as demonstrated by CD45 RNA expression analyzed in parallel. Thus, the mHag HA-1 can function as an excellent target antigen for immunotherapy of hematological malignancies with no or low risk of GvHD.
D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000150:complications / Q000473:pathology* / Q000628:therapy; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D015778:Minor Histocompatibility Antigens / Q000032:analysis / Q000235:genetics*; D009842:Oligopeptides / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis*; D014018:Tissue Distribution
C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens