title: Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model.
abstract: The prognosis of malignant gliomas remains dismal and alternative therapeutic strategies are required. Immunotherapy with dendritic cells (DCs) pulsed with tumour antigens emerges as a promising approach. Many parameters influence the efficacy of DC-based vaccines and need to be optimised in preclinical models. The present study compares different vaccine schedules using DCs loaded with tumour cell lysate (DC-Lysate) for increasing long-term survival in the GL26 orthotopic murine glioma model, focusing on the number of injections and an optimal way to recall antitumour immune response. Double vaccination with DC-Lysate strongly prolonged median survival compared to unvaccinated animals (mean survival 87.5 days vs. 25 days; p < 0.0001). In vitro data showed specific cytotoxic activity against GL26. However, late tumour relapses frequently occurred after 3 months and only 20% of mice were finally cured at 7 months. While one, two or three DC injections gave identical survival, a boost using only tumour lysate after initial DC-Lysate priming dramatically improved long-term survival in vaccinated mice, compared to the double DC-Lysate group, with 67.5% of animals cured at 7 months (p < 0.0001). In vitro data showed better specific CTL response and also the induction of specific anti-GL26 antibodies in the DC-Lysate/Lysate group, which mediated Complement Dependent Cytotoxicity. These experimental data may be of importance for the design of clinical trials that currently use multiple DC injections.
authors.affiliation: Neurosurgery department, Neurological and Neurosurgical Hospital Pierre Wertheimer, Claude Bernard University, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Jouanneau
authors.forename: D
authors.initials: D
authors.lastname: Poujol
authors.forename: S
authors.initials: S
authors.lastname: Gulia
authors.forename: I
authors.initials: I
authors.lastname: Le Mercier
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.forename: M F
authors.initials: MF
authors.lastname: Belin
authors.forename: I
authors.initials: I
authors.lastname: Puisieux
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines