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BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide

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Abstract

B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to enhance humoral responses following vaccination has not been evaluated. We evaluated BLyS serum levels and antigen-specific antibody titers in 8 patients undergoing therapeutic temozolomide (TMZ)-induced lymphopenia, with concomitant vaccine against a tumor-specific mutation in the epidermal growth factor receptor (EGFRvIII). Our studies demonstrate that TMZ-induced lymphopenia corresponded with spikes in serum BLyS that directly preceded the induction of anti-EGFRvIII antigen-specific antibody titers, in some cases as high as 1:2,000,000. Our data are the first clinical observation of BLyS serum elevation and greatly enhanced humoral immune responses as a consequence of chemotherapy-induced lymphopenia. These observations should be considered for the development of future vaccination strategies in the setting of malignancy.

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Acknowledgments

The authors would like to thank Tecca Wright and Tracy A. Chewning for their assistance in the preparation of grant applications supporting these studies. In addition, special thanks go to Shicheng Yang, MD, PhD, Carter Suryadevara, and Tony Shan for their contribution on data discussion.

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All other authors do not have any conflict of interest.

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Correspondence to John H. Sampson.

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Sanchez-Perez, L., Choi, B.D., Reap, E.A. et al. BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide. Cancer Immunol Immunother 62, 983–987 (2013). https://doi.org/10.1007/s00262-013-1405-y

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