title: 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.affiliation: Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Perez
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Choi
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Reap
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Sayour
authors.forename: Pamela
authors.initials: P
authors.lastname: Norberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schmittling
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Archer
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Duane A
authors.initials: DA
authors.lastname: Mitchell
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
mesh_terms: D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity / Q000276:immunology; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood*; D019496:Cancer Vaccines / Q000276:immunology*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005909:Glioblastoma / Q000276:immunology* / Q000628:therapy; D006801:Humans; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000097:blood / Q000139:chemically induced; D000077204:Temozolomide
chemical_list: D000906:Antibodies; D018906:Antineoplastic Agents, Alkylating; D053264:B-Cell Activating Factor; D019496:Cancer Vaccines; D003606:Dacarbazine; D000077204:Temozolomide