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

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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.

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Acknowledgments

This work was supported by a Multiple Myeloma Research Foundation Fellow Award (LDA), an ASCO Young Investigator Award (LDA), an NIH K12 Career Development Award (LDA), an American Cancer Society Institutional Research Grant (LDA), and NIH grants CA18029 and 114536 (SRR).

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No conflicts of interest to disclose.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

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

  2. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8565, USA

    Larry D. Anderson Jr.

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  1. Larry D. Anderson Jr.
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  2. Danielle R. Cook
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  3. Tori N. Yamamoto
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  6. Stanley R. Riddell
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Correspondence to Larry D. Anderson Jr..

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Anderson, L.D., Cook, D.R., Yamamoto, T.N. et al. Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma. Cancer Immunol Immunother 60, 985–997 (2011). https://doi.org/10.1007/s00262-011-1009-3

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