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01-03-2006 | Original Article

Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model

Authors: E. Jouanneau, D. Poujol, S. Gulia, I. Le Mercier, J. Y. Blay, M. F. Belin, I. Puisieux

Published in: Cancer Immunology, Immunotherapy | Issue 3/2006

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 daysvs. 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.

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Title: Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model
Authors: E. Jouanneau
D. Poujol
S. Gulia
I. Le Mercier
J. Y. Blay
M. F. Belin
I. Puisieux
Publication date: 01-03-2006
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 3/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-005-0040-7

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