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Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

Publication ,  Journal Article
Heimberger, AB; Crotty, LE; Archer, GE; Hess, KR; Wikstrand, CJ; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
Published in: Clin Cancer Res
September 15, 2003

PURPOSE: The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. EXPERIMENTAL DESIGN: C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. RESULTS: S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P < 0.05). PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P < 0.05). In vivo depletion studies showed that the effector cell population was natural killer and CD8+ T cells, and in vitro assays showed that macrophages could lyse target tumor cells with serum from the PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). CONCLUSIONS: Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The therapeutic effect of peptide vaccination may be mediated, in part, by antibody-dependent cellular cytotoxicity.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 15, 2003

Volume

9

Issue

11

Start / End Page

4247 / 4254

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Rate
  • Spleen
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice, Inbred C3H
  • Mice
  • Melanoma, Experimental
  • Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Heimberger, A. B., Crotty, L. E., Archer, G. E., Hess, K. R., Wikstrand, C. J., Friedman, A. H., … Sampson, J. H. (2003). Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res, 9(11), 4247–4254.
Heimberger, Amy B., Laura E. Crotty, Gary E. Archer, Kenneth R. Hess, Carol J. Wikstrand, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, and John H. Sampson. “Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.Clin Cancer Res 9, no. 11 (September 15, 2003): 4247–54.
Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, Friedman AH, et al. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res. 2003 Sep 15;9(11):4247–54.
Heimberger, Amy B., et al. “Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.Clin Cancer Res, vol. 9, no. 11, Sept. 2003, pp. 4247–54.
Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, Friedman AH, Friedman HS, Bigner DD, Sampson JH. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res. 2003 Sep 15;9(11):4247–4254.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 15, 2003

Volume

9

Issue

11

Start / End Page

4247 / 4254

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Rate
  • Spleen
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice, Inbred C3H
  • Mice
  • Melanoma, Experimental
  • Lymphocytes