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.
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5 August 2002
Article|
August 05 2002
The Hematopoietic System–specific Minor Histocompatibility Antigen HA-1 Shows Aberrant Expression in Epithelial Cancer Cells
Christoph A. Klein,
Christoph A. Klein
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Martina Wilke,
Martina Wilke
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
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Jos Pool,
Jos Pool
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
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Corine Vermeulen,
Corine Vermeulen
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
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Els Blokland,
Els Blokland
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
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Elke Burghart,
Elke Burghart
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Sabine Krostina,
Sabine Krostina
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Nicole Wendler,
Nicole Wendler
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Bernward Passlick,
Bernward Passlick
2Chirurgische Klinik, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Gert Riethmüeller,
Gert Riethmüeller
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
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Els Goulmy
Els Goulmy
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
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Christoph A. Klein
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Martina Wilke
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
Jos Pool
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
Corine Vermeulen
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
Els Blokland
3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
Elke Burghart
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Sabine Krostina
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Nicole Wendler
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Bernward Passlick
2Chirurgische Klinik, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Gert Riethmüeller
1Department of Immunology, Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich, Germany
Els Goulmy
3Department 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: [email protected]
C.A. Klein and M. Wilke contributed equally to this work.
*
Abbreviations used in this paper: CGH, comparative genomic hybridization; LCL, lymphocyte cell line; mHag, minor histocompatibility antigen; PBGD, porphobilinogen deaminase; SCT, stem cell transplantation.
Received:
November 05 2001
Revision Received:
June 10 2002
Accepted:
June 20 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (3): 359–368.
Article history
Received:
November 05 2001
Revision Received:
June 10 2002
Accepted:
June 20 2002
Citation
Christoph A. Klein, Martina Wilke, Jos Pool, Corine Vermeulen, Els Blokland, Elke Burghart, Sabine Krostina, Nicole Wendler, Bernward Passlick, Gert Riethmüeller, Els Goulmy; The Hematopoietic System–specific Minor Histocompatibility Antigen HA-1 Shows Aberrant Expression in Epithelial Cancer Cells . J Exp Med 5 August 2002; 196 (3): 359–368. doi: https://doi.org/10.1084/jem.20011838
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