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Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model.
Cancer Immunol Immunother 2005; 54(2):107-19CI

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-gamma 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 F98(EGFRvIII) cells was attenuated in vaccinated rats; whereas, growth of F98(EGFR) cells was not. The median survival of vaccinated rats was increased 72% over that of unvaccinated controls challenged with intracerebral F98(EGFRvIII) 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.

Authors+Show Affiliations

Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Michael.Ciesielski@RoswellPark.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15340764

Citation

Ciesielski, Michael J., et al. "Cellular Antitumor Immune Response to a Branched Lysine Multiple Antigenic Peptide Containing Epitopes of a Common Tumor-specific Antigen in a Rat Glioma Model." Cancer Immunology, Immunotherapy : CII, vol. 54, no. 2, 2005, pp. 107-19.
Ciesielski MJ, Kazim AL, Barth RF, et al. Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model. Cancer Immunol Immunother. 2005;54(2):107-19.
Ciesielski, M. J., Kazim, A. L., Barth, R. F., & Fenstermaker, R. A. (2005). Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model. Cancer Immunology, Immunotherapy : CII, 54(2), pp. 107-19.
Ciesielski MJ, et al. Cellular Antitumor Immune Response to a Branched Lysine Multiple Antigenic Peptide Containing Epitopes of a Common Tumor-specific Antigen in a Rat Glioma Model. Cancer Immunol Immunother. 2005;54(2):107-19. PubMed PMID: 15340764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular antitumor immune response to a branched lysine multiple antigenic peptide containing epitopes of a common tumor-specific antigen in a rat glioma model. AU - Ciesielski,Michael J, AU - Kazim,A Latif, AU - Barth,Rolf F, AU - Fenstermaker,Robert A, Y1 - 2004/08/31/ PY - 2004/04/19/received PY - 2004/05/28/accepted PY - 2004/9/2/pubmed PY - 2005/2/4/medline PY - 2004/9/2/entrez SP - 107 EP - 19 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 54 IS - 2 N2 - 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-gamma 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 F98(EGFRvIII) cells was attenuated in vaccinated rats; whereas, growth of F98(EGFR) cells was not. The median survival of vaccinated rats was increased 72% over that of unvaccinated controls challenged with intracerebral F98(EGFRvIII) 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. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/15340764/Cellular_antitumor_immune_response_to_a_branched_lysine_multiple_antigenic_peptide_containing_epitopes_of_a_common_tumor_specific_antigen_in_a_rat_glioma_model_ L2 - https://dx.doi.org/10.1007/s00262-004-0576-y DB - PRIME DP - Unbound Medicine ER -