The hematopoietic system-specific minor histocompatibility antigen HA-1 shows aberrant expression in epithelial cancer cells

J Exp Med. 2002 Aug 5;196(3):359-68. doi: 10.1084/jem.20011838.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy
  • Leukocyte Common Antigens / genetics
  • Minor Histocompatibility Antigens / genetics*
  • Minor Histocompatibility Antigens / immunology
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / therapy
  • Oligopeptides / genetics*
  • Oligopeptides / immunology
  • RNA, Messenger / analysis
  • T-Lymphocytes, Cytotoxic / immunology
  • Transcription, Genetic
  • Transplantation, Homologous
  • Tumor Cells, Cultured

Substances

  • HA-1 antigen
  • Minor Histocompatibility Antigens
  • Oligopeptides
  • RNA, Messenger
  • Leukocyte Common Antigens