Related Experiment Videos
DNA vaccines against HPV-16 E7-expressing tumour cells
Federico De Marco1, Sophie Hallez, Jean Marc Brulet
1Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi D'Oro 156, 00158, Rome, Italy.
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.