DNA vaccines against HPV-16 E7-expressing tumour cells

Abstract

Background: Genetic immunisation induces the endogenous production of the encoded antigens, which favours their presentation by MHC class I molecules. The E7 protein from "high risk" Human Papillomavirus (HPV) is constitutively expressed in cervical cancer and represents a target for immunotherapy.

Materials and methods: Several E7-encoding DNA vaccines were constructed including unmodified E7 and E7 fused to ubiquitin or to the Invariant chain in order to increase the presentation of E7-derived peptides by MHC class I or II molecules, respectively. These vaccines were administered i.m. to C57BL/6 mice that were subsequently challenged with E7-positive tumour cell lines expressing different levels of MHC class I molecules.

Results: The E7-Ii fusion sequence protected a number of animals from tumour challenging. No differences were associated with the MHC class I status of the challenging cell lines.

Conclusion: Engineering the intracellular pathway for antigen presentation is able to produce a valid therapeutic response even against tumours with down-regulated MHC class I.