Search

Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered the application of a replication-defective recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. In preclinical studies, we demonstrated that recombinant SFV (rSFV) encoding HPV E6 and E7 (rSFVeE6,7), induces robust HPV-specific cellular immune and memory responses upon intramuscular (i.m.) administration in mice resulting in excellent therapeutic anti-tumour efficacy. Despite the clear potency of the SFV vector system, there are a number of inherent challenges. These include manufacturing costs, shelf-life and anti-vector responses. DNA vaccination is an alternative method with the potential to be inexpensive and safe. In this project, the drawbacks associated with both SFV-based vaccines and DNA vaccines are circumvented with the development of a DNA vaccine based on the SFV replicase (DREP). This next generation vaccine will exploit the advantages of both strategies for the development of an immunotherapeutic response against cervical neoplasia by encoding the fusion protein eE6,7 (DREPeE6,7). Our initial results show that upon intradermal delivery via electroporation of mice with DREP-eE6,7, similar E7-specific responses were elicited as compared to i.m. administration of rSFVeE6,7. These results will be further confirmed for assessment of therapeutic efficacy using a TC-1 tumor model.

Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered the application of a replication-defective recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. In preclinical studies, we demonstrated that recombinant SFV (rSFV) encoding HPV E6 and E7 (rSFVeE6,7), induces robust HPV-specific cellular immune and memory responses upon intramuscular (i.m.) administration in mice resulting in excellent therapeutic anti-tumour efficacy. Despite the clear potency of the SFV vector system, there are a number of inherent challenges. These include manufacturing costs, shelf-life and anti-vector responses. DNA vaccination is an alternative method with the potential to be inexpensive and safe. In this project, the drawbacks associated with both SFV-based vaccines and DNA vaccines are circumvented with the development of a DNA vaccine based on the SFV replicase (DREP). This next generation vaccine will exploit the advantages of both strategies for the development of an immunotherapeutic response against cervical neoplasia by encoding the fusion protein eE6,7 (DREPeE6,7). Our initial results show that upon intradermal delivery via electroporation of mice with DREP-eE6,7, similar E7-specific responses were elicited as compared to i.m. administration of rSFVeE6,7. These results will be further confirmed for assessment of therapeutic efficacy using a TC-1 tumor model.