Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions

Yoshiki Akatsuka, Yasuo Morishima, Kiyotaka Kuzushima, Yoshihisa Kodera, Toshitada Takahashi

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versus-leukemia/ lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed self-proteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalCancer science
Volume98
Issue number8
DOIs
Publication statusPublished - 01-08-2007

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Minor Histocompatibility Antigens
Immunotherapy
Cell Transplantation
Graft vs Host Disease
Antigens
Single Nucleotide Polymorphism
Lymphoma
Leukemia
Tissue Donors
Transplants
Adoptive Immunotherapy
Neoplasms
Peptide Fragments
Isoantigens
Homologous Transplantation
Graft Rejection
Neoplasm Antigens
Hematologic Neoplasms
HLA Antigens
Major Histocompatibility Complex

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Akatsuka, Yoshiki ; Morishima, Yasuo ; Kuzushima, Kiyotaka ; Kodera, Yoshihisa ; Takahashi, Toshitada. / Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions. In: Cancer science. 2007 ; Vol. 98, No. 8. pp. 1139-1146.
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Akatsuka, Y, Morishima, Y, Kuzushima, K, Kodera, Y & Takahashi, T 2007, 'Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions', Cancer science, vol. 98, no. 8, pp. 1139-1146. https://doi.org/10.1111/j.1349-7006.2007.00521.x

Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions. / Akatsuka, Yoshiki; Morishima, Yasuo; Kuzushima, Kiyotaka; Kodera, Yoshihisa; Takahashi, Toshitada.

In: Cancer science, Vol. 98, No. 8, 01.08.2007, p. 1139-1146.

Research output: Contribution to journalReview article

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AU - Akatsuka, Yoshiki

AU - Morishima, Yasuo

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AU - Kodera, Yoshihisa

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