Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma

Larry D. Anderson, Danielle R. Cook, Tori N. Yamamoto, Carolina Berger, David G. Maloney, Stanley R. Riddell

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Multiple myeloma is incurable with standard therapies but is susceptible to a T-cell-mediated graft versus myeloma effect after allogeneic stem cell transplantation. We sought to identify myeloma-specific antigens that might be used for T-cell immunotherapy of myeloma. MAGE-C1 (CT-7) is a cancer-testis antigen that is expressed by tumor cells in >70% of myeloma patients and elicits a humoral response in up to 93% of patients with CT-7+ myeloma. No CD8+ T-cell epitopes have been described for CT-7, so we used a combination of reverse immunology and immunization of HLA-A2 transgenic mice with a novel cell-based vaccine to identify three immunogenic epitopes of CT-7 that are recognized by human CD8+ T-cells. CT-7-specific T-cells recognizing two of these peptides are able to recognize myeloma cells as well as CT-7 gene-transduced tumor cells, demonstrating that these epitopes are naturally processed and presented by tumor cells. This is the first report of the identification of immunogenic CD8+ T-cell epitopes of MAGE-C1 (CT-7), which is the most commonly expressed cancer-testis antigen found in myeloma, and these epitopes may be promising candidate targets for vaccination or T-cell therapy of myeloma or other CT-7+ malignancies.

Original languageEnglish (US)
Pages (from-to)985-997
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume60
Issue number7
DOIs
StatePublished - Jul 1 2011

Keywords

  • CT-7
  • Cancer immunology
  • Immunotherapy
  • MAGE-C1
  • Multiple myeloma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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