Cancer Immunology, Immunotherapy

, Volume 60, Issue 7, pp 985–997

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

  • Larry D. AndersonJr.
  • Danielle R. Cook
  • Tori N. Yamamoto
  • Carolina Berger
  • David G. Maloney
  • Stanley R. Riddell
Original Article

DOI: 10.1007/s00262-011-1009-3

Cite this article as:
Anderson, L.D., Cook, D.R., Yamamoto, T.N. et al. Cancer Immunol Immunother (2011) 60: 985. doi:10.1007/s00262-011-1009-3

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.

Keywords

MAGE-C1CT-7Multiple myelomaCancer immunologyImmunotherapy

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Larry D. AndersonJr.
    • 1
    • 2
  • Danielle R. Cook
    • 1
  • Tori N. Yamamoto
    • 1
  • Carolina Berger
    • 1
  • David G. Maloney
    • 1
  • Stanley R. Riddell
    • 1
  1. 1.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Simmons Comprehensive Cancer CenterUT Southwestern Medical CenterDallasUSA