The Immunogenicity and Anti-Tumor Efficacy of a Rationally Designed EGFR Vaccine

Abstract

Background/Aims: The abnormally activated EGFR promotes tumor growth, invasion and metastasis. Current therapeutics targeting EGFR have markedly improved the clinical outcome, but they are limited in use due to transient efficacy, frequent administration, high cost and significant toxicity. Methods: We rationally designed a multiepitope immunogen against EGFR, named as DEGFRm. The immunogen is composed of an epitope peptide (EGFR265-283) and the extracellular domain III (EGFR334-505) of mouse EGFR. EGFR265-283 is grafted onto the translocation domain of diphtheria toxin (DTT), and EGFR334-505 is fused to C-terminal of DTT. Next, the immunogenicity and anti-tumor efficacies of DEGFRm vaccine were examined in mouse tumor models. Results: When formulated with Alum and CpG, DEGFRm vaccine elicits Th 1 immune responses and inhibits tumor growth in both prophylactic and therapeutic mouse tumor models. Moreover, the tumor microvasculature is markedly reduced and the tumor infiltration of CD8+ T lymphocytes is greatly enhanced. Conclusions: These data suggest that active immunization with DEGFRm vaccine is a promising strategy for therapy of various EGFR+ cancers.

Keywords

• Cancer vaccine
• EGFR
• Diphtheria toxin T-domain
• CpG