title: Treatment of a patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Case Report.
abstract: Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I-matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic encephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.
authors.affiliation: Division of Neurosurgery, Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-6901, USA. lliau@mednet.ucla.edu
authors.forename: L M
authors.initials: LM
authors.lastname: Liau
authors.forename: K L
authors.initials: KL
authors.lastname: Black
authors.forename: N A
authors.initials: NA
authors.lastname: Martin
authors.forename: S N
authors.initials: SN
authors.lastname: Sykes
authors.forename: J M
authors.initials: JM
authors.lastname: Bronstein
authors.forename: L
authors.initials: L
authors.lastname: Jouben-Steele
authors.forename: P S
authors.initials: PS
authors.lastname: Mischel
authors.forename: A
authors.initials: A
authors.lastname: Belldegrun
authors.forename: T F
authors.initials: TF
authors.lastname: Cloughesy
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D017809:Fatal Outcome; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I