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Updated: Aug 30, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors
Amy B Heimberger1, Laura E Crotty, Gary E Archer
1Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Unit 442, 1515 Holcombe Boulevard, Houston, TX 77030, USA. aheimber@mdanderson.org
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.
Insights
This study demonstrates that a vaccine targeting the EGFRvIII mutation (PEP-3-KLH) effectively prevents and treats tumors in mouse models. The vaccine shows significant efficacy against both subcutaneous and intracerebral tumors, increasing survival rates.
Area of Science:
- Oncology
- Immunology
- Cancer Vaccines
Background:
- Epidermal growth factor receptor (EGFR) amplification and mutations, particularly EGFRvIII, are common in malignant gliomas and other cancers.
- EGFRvIII represents a tumor-specific target for therapeutic intervention.
Purpose of the Study:
- To evaluate the efficacy of a novel vaccine (PEP-3-KLH) targeting the EGFRvIII mutation in preclinical mouse models.
- To assess the vaccine's effectiveness against both the development and established forms of EGFRvIII-expressing tumors.
Main Methods:
- Mice were vaccinated with PEP-3-KLH (EGFRvIII peptide conjugated to keyhole limpet hemocyanin) or KLH alone.
- Mice were challenged with syngeneic melanoma cells expressing a murine homologue of EGFRvIII, both subcutaneously (s.c.) and intracerebrally.
- Studies included evaluating tumor development, growth, survival rates, and immune responses (antibody titers, cellular cytotoxicity).
Main Results:
- PEP-3-KLH vaccination prevented tumor development in 70% of mice and reduced tumor size in others.
- Significant increases in median survival time were observed for both prophylactic and therapeutic vaccination against intracerebral tumors (>173% and 26% increase, respectively).
- Antibody titers against PEP-3 were enhanced, and passive transfer of immune sera conferred protection, suggesting an antibody-mediated mechanism.
Conclusions:
- Vaccination with an EGFRvIII-specific peptide (PEP-3-KLH) demonstrates significant therapeutic efficacy against both subcutaneous and established intracerebral tumors.
- The anti-tumor effects appear to be mediated, at least in part, by antibody-dependent cellular cytotoxicity involving natural killer cells, CD8+ T cells, and macrophages.
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