The hematopoietic system-specific minor histocompatibility antigen HA-1 shows aberrant expression in epithelial cancer cells.
Allogeneic stem cell transplantation (SCT) can induce curative graft-versus-tumor reactions in patients with hematological malignancies and solid tumors. The graft-versus-tumor reaction after human histocompatibility leukocyte antigen (HLA)-identical SCT is mediated by alloimmune donor T cells specific for polymorphic minor histocompatibility antigens (mHags). Among these, the mHag HA-1 was found to be restricted to the hematopoietic system. Here, we report on the HA-1 ribonucleic acid expression by microdissected carcinoma tissues and by single disseminated tumor cells isolated from patients with various epithelial tumors. The HA-1 peptide is molecularly defined, as it forms an immunogenic peptide ligand with HLA-A2 on the cell membrane of carcinoma cell lines. HA-1-specific cytotoxic T cells lyse epithelial tumor cell lines in vitro, whereas normal epithelial cells are not recognized. Thus, HA-1-specific immunotherapy combined with HLA-identical allogeneic SCT may now be feasible for patients with HA-1(+) carcinomas.
Klein
Christoph A
CA
Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany. E.A.J.M.Goulmy@lumc.nl
Wilke
Martina
M
Pool
Jos
J
Vermeulen
Corine
C
Blokland
Els
E
Burghart
Elke
E
Krostina
Sabine
S
Wendler
Nicole
N
Passlick
Bernward
B
Riethmüeller
Gert
G
Goulmy
Els
E
D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D017493:Leukocyte Common Antigens / Q000235:genetics; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000628:therapy; D009842:Oligopeptides / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured
C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens