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The Hematopoietic System–specific Minor Histocompatibility Antigen HA-1 Shows Aberrant Expression in Epithelial Cancer Cells

Christoph A. Klein¹, Martina Wilke³, Jos Pool³, Corine Vermeulen³, Els Blokland³, Elke Burghart¹, Sabine Krostina¹, Nicole Wendler¹, Bernward Passlick², Gert Riethmüeller¹ and Els Goulmy³

¹ Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
² Chirurgische Klinik, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
³ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

Address correspondence to Els Goulmy, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands. Phone: 31-71-526-1966; Fax: 31-71-521-6751; E-mail: E.A.J.M.Goulmy{at}lumc.nl

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.

Key Words: stem cell transplantation • graft-versus-tumor • carcinomas • cytotoxic T cells • minimal residual disease

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