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Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma

Nature Medicine volume 11, pages 986–991 (2005)Cite this article

Abstract

The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell–dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance1,2,3,4, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory5,6,7. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody–based chemotherapy of mantle cell lymphoma in first remission. Humoral antigen- and tumor-specific responses were detectable but delayed, and they correlated with peripheral blood B-cell recovery. In contrast, vigorous CD4+ and CD8+ antitumor type I T-cell cytokine responses were induced in most individuals in the absence of circulating B cells. Analysis of relapsing tumors showed no mutations or change in expression of target antigen to explain escape from therapy. These results show that severe B-cell depletion does not impair T-cell priming in humans. Based on these results, it is justifiable to administer vaccines in the setting of B-cell depletion; however, vaccine boosts after B-cell recovery may be necessary for optimal humoral responses.

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Figure 1: Peripheral blood B-cell dynamics and humoral responses.
Figure 2: Tumor-specific cellular immune responses were induced in 20 of 23 individuals by vaccination.
Figure 3: Tumor-specific CD4+ and CD8+ T-cell responses were detected by intracellular cytokine assay.

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Acknowledgements

We thank the physicians, pharmacy and nursing staff of the 13E unit in Building 10, National Institutes of Health Clinical Center, for their patient care. We thank A. Malyguine, S. Strobl and K. Shafer-Weaver for performing the ELISPOT assays and Amgen for providing the sCD40Lt. We also thank the patients for participating in this trial. We thank A. Woo for editorial assistance and J. Horton and M. Ferraro for help with data management.

Author information

Author notes

  1. Sattva S Neelapu & Larry W Kwak

    Present address: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 429, Houston, Texas, 77030, USA

Authors and Affiliations

  1. Experimental and Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, 20892, Maryland, USA

    Sattva S Neelapu, Larry W Kwak, John E Janik, Kieron Dunleavy, Therese White, Maryalice Stetler-Stevenson, Elaine S Jaffe, Ronald Gress, Fran Hakim & Wyndham H Wilson

  2. SAIC, NCI-Frederick, 1050 Boyles Street, Frederick, 21702, Maryland, USA

    Carol B Kobrin, Linda Harvey & Robin Pennington

  3. Office of Scientific Operations, NCI-Frederick, 1050 Boyles Street, Frederick, 21702, Maryland, USA

    Craig W Reynolds

  4. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, 20892, Maryland, USA

    Seth M Steinberg

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  1. Sattva S Neelapu
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Corresponding author

Correspondence to Larry W Kwak.

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Competing interests

Larry W. Kwak is a consultant for Accentia Biopharmaceuticals, which developed the vaccine product used in the study. Although Accentia did not sponsor this study, the company may gain from results presented herein.

Supplementary information

Supplementary Fig. 1

Peripheral blood T-cell dynamics. (PDF 66 kb)

Supplementary Fig. 2

Tumor-specific immune responses in postvaccine PBMCs were associated with both human leukocyte antigen (HLA) class I and class II molecules. (PDF 69 kb)

Supplementary Fig. 3

Postvaccine PBMCs specifically recognized autologous idiotype protein. (PDF 65 kb)

Supplementary Fig. 4

Persistence of target antigen at relapse. (PDF 63 kb)

Supplementary Note (PDF 31 kb)

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Neelapu, S., Kwak, L., Kobrin, C. et al. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med 11, 986–991 (2005). https://doi.org/10.1038/nm1290

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