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  • Original Article
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Allografting

Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma

Bone Marrow Transplantation volume 36, pages 315–323 (2005)Cite this article

Summary:

The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy. Our objective was to induce tumor-specific T-cell immunity in bone marrow transplant (BMT) donors to enhance antitumor effects of allografts. We vaccinated five HLA-matched sibling donors with myeloma Id proteins isolated from recipient plasma before bone marrow harvest. Recipients were administered booster Id immunizations following transplantation. Vaccination induced donor Id and carrier-specific cellular and/or humoral immune responses. Two recipients died within 30 days of BMT from transplant-related complications. Id and carrier-specific T-cell responses were detected in all three remaining patients post-, but not pre-BMT and persisted for 18 months. All three surviving patients converted from partial to complete responses following BMT. Two of the three patients remain disease-free 7 years and 8 years after BMT, and the third died of renal failure after 5.5 years while in complete remission from myeloma. Our results suggest that myeloma Id vaccination induces specific T-cell immunity in healthy donors which may be transferable by BMT, is associated with prolonged disease-free survival of recipients, and may represent a general strategy to enhance graft-versus-tumor effect in other malignancies for which defined tumor-specific antigens exist.

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Acknowledgements

We thank the physicians, pharmacy and nursing staff of the 13E unit in Building 10, NIH Clinical Center, and of the University of Arkansas Medical Sciences for their patient care. We also thank the patients for participating in this trial. This publication has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Author notes

  1. N C Munshi

    Present address: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

  2. S Jagannath

    Present address: St Vincents Hospital Manhattan Center, New York, NY, USA

Authors and Affiliations

  1. Experimental and Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    S S Neelapu, T M Watson & L W Kwak

  2. The Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    N C Munshi, S Jagannath & B Barlogie

  3. Science Applications International Corporation, NCI-Frederick, Frederick, MD, USA

    R Pennington

  4. Office of Scientific Operations, NCI-Frederick, Frederick, MD, USA

    C Reynolds

Authors
  1. S S Neelapu
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Correspondence to L W Kwak.

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Neelapu, S., Munshi, N., Jagannath, S. et al. Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma. Bone Marrow Transplant 36, 315–323 (2005). https://doi.org/10.1038/sj.bmt.1705057

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