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.