Background: Cervical and other anogenital cancers account for ~ 5% of the global cancer burden, generally caused by persistent infection with human papillomavirus (HPV). HPV vaccines that can prevent high risk HPV infection have the potential to prevent HPV related cervical and other cancers. However, development of effective HPV specific immunotherapy to treat existing HPV infection and associated invasive cancers has proven challenging, despite the expression by these tumours of well-defined virus derived tumour-associated antigens, and more research is need into antigen delivery systems including adjuvants that can invoke effective immune responses against these well-defined tumour antigens. We have developed one nano-adjuvant, which we hypothesise will perform better for immunotherapy  

Results: Our nano-adjuvant induced strong intracellular reactive oxygen species (ROS) in bone marrow derived macrophages (BMMs). Furthermore, the nano-adjuvant showed endo/lysosome escape capability in BMMs by consuming H+ in endo/lysosomes and achieve membrane disruption to deliver E7 antigen into the cytosolic major histocompatibility I pathway. Mice immunised with HPV16E7 peptide GF001 (RAHYNIVTF) loaded nano-adjuvant developed strong E7 specific CD8+ T cell responses.  Immunising mice with Quil A+E7 peptide  prior to challenge with E7 expressing TC-1 tumour resulted in reduced tumour growth compared with unimmunised mice,  with 1/5 mice  tumour free at Day 30. In contrast, mice immunised with our nano-adjuvant+E7 peptide grew  tumour  slowly from day 0 to 12 and the tumour then regressed, with 5/5 mice tumour-free at Day 30. In future work, this nano-adjuvant will be evaluated as therapy for existing TC-1 tumours, and our hypothesis that intracellular ROS-mediated inflammatory signalling pathway via NLRP3 inflammasome may account for our nano-adjuvant efficacy will be tested.