title: Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients.
abstract: Cancer vaccine trials have failed to yield robust immune-correlated clinical improvements as observed in animal models, fueling controversy over the utility of human cancer vaccines. Therapeutic vaccination represents an intriguing additional therapy for glioblastoma multiforme (GBM; grade 4 glioma), which has a dismal prognosis and treatment response, but only early phase I vaccine trial results have been reported. Immune and clinical responses from a phase II GBM vaccine trial are reported here. IFN-gamma responsiveness was quantified in peripheral blood of 32 GBM patients given therapeutic dendritic cell vaccines. Posttreatment times to tumor progression (TTP) and survival (TTS) were compared in vaccine responders and nonresponders and were correlated with immune response magnitudes. GBM patients (53%) exhibited >or=1.5-fold vaccine-enhanced cytokine responses. Endogenous antitumor responses of similar magnitude occurred in 22% of GBM patients before vaccination. Vaccine responders exhibited significantly longer TTS and TTP relative to nonresponders. Immune enhancement in vaccine responders correlated logarithmically with TTS and TTP spanning postvaccine chemotherapy, but not with initial TTP spanning vaccination alone. This is the first report of a progressive correlation between cancer clinical outcome and T-cell responsiveness after therapeutic vaccination in humans and the first tracing of such correlation to therapeutically exploitable tumor alteration. As such, our findings offer unique opportunities to identify cellular and molecular components of clinically meaningful antitumor immunity in humans.
authors.affiliation: Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA. wheelerc@cshs.org
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wheeler
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: Gentao
authors.initials: G
authors.lastname: Liu
authors.forename: Mia
authors.initials: M
authors.lastname: Mazer
authors.forename: Xiao-xue
authors.initials: XX
authors.lastname: Zhang
authors.forename: Samuel
authors.initials: S
authors.lastname: Pepkowitz
authors.forename: Dennis
authors.initials: D
authors.lastname: Goldfinger
authors.forename: Hiushan
authors.initials: H
authors.lastname: Ng
authors.forename: Dwain
authors.initials: D
authors.lastname: Irvin
authors.forename: John S
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D001932:Brain Neoplasms / Q000382:microbiology* / Q000628:therapy*; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007107:Immune System; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines