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

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.

• Authors: Luis Sanchez-Perez, Bryan D Choi, Elizabeth A Reap, Elias J Sayour, Pamela Norberg, Robert J Schmittling, Gerald E Archer, James E Herndon 2nd, Duane A Mitchell, Amy B Heimberger, Darell D Bigner, John H Sampson
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 62 Issue 6 Pg. 983-7 (Jun 2013) ISSN: 1432-0851 [Electronic] Germany
• PMID: 23591978 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Antineoplastic Agents, Alkylating
• B-Cell Activating Factor
• Cancer Vaccines
• Dacarbazine
• Temozolomide

Topics

• Antibodies (blood)
• Antibody Specificity (immunology)
• Antineoplastic Agents, Alkylating (adverse effects, therapeutic use)
• B-Cell Activating Factor (blood)
• Cancer Vaccines (immunology)
• Dacarbazine (adverse effects, analogs & derivatives, therapeutic use)
• Glioblastoma (immunology, therapy)
• Humans
• Lymphocyte Depletion
• Lymphopenia (blood, chemically induced)
• Temozolomide