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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 2/2005

01-02-2005 | Original Article

Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model

Authors: Michael J. Ciesielski, A. Latif Kazim, Rolf F. Barth, Robert A. Fenstermaker

Published in: Cancer Immunology, Immunotherapy | Issue 2/2005

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Abstract

Human malignant gliomas contain epidermal growth factor receptor (EGFR) gene mutations that encode tumor-associated antigens (TAAs) that can be targeted using immunological techniques. One EGFR mutant gene (EGFRvIII) encodes a protein with an epitope that is not found in normal tissues. A number of studies have focused on this unique epitope as a potential target for tumor vaccines. In the present study, we examined the cellular immune effects of a peptide containing multiple copies of the unique EGFRvIII epitope linked together by way of a lysine bridge. Fischer rats were vaccinated with an EGFRvIII multiple antigenic peptide (MAP). While vaccination produced a humoral immune response, anti-MAP antibody production was not accompanied by expression of the Th2 response cytokine IL-4. In MAP/GM-CSF vaccinated animals, a cellular immune response was detected in association with the appearance of CD4+ and CD8+ T cells at the tumor site. Splenocytes and CD8+ T cells from vaccinated rats produced the Th1 cytokine IFN-γ in vitro in response to stimulation by rat glioma cells expressing EGFRvIII, but not by those expressing wild-type EGFR. MAP vaccine also induced a specific lytic antitumor CTL immune response against F98 glioma cells expressing EGFRvIII, but not against F98 cells expressing either wild-type EGFR or no receptor. The in vivo growth of F98EGFRvIII cells was attenuated in vaccinated rats; whereas, growth of F98EGFR cells was not. The median survival of vaccinated rats was increased 72% over that of unvaccinated controls challenged with intracerebral F98EGFRvIII tumor implants. Therefore, MAP vaccination produced a predominantly cellular antitumor immune response directed against F98 gliomas expressing the EGFRvIII target antigen. The potent immunosuppressive effects of F98 glioma cells mimic the human disease and make this particular tumor model useful for studying immunotherapeutic approaches to malignant gliomas.
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Metadata
Title
Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model
Authors
Michael J. Ciesielski
A. Latif Kazim
Rolf F. Barth
Robert A. Fenstermaker
Publication date
01-02-2005
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 2/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0576-y

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