Under the optimistic assumption of high-prophylactic
HPV vaccine coverage, a significant reduction of
cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic
vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7
oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human
cancers. New strategies/technologies have been developed to improve these therapeutic
vaccines. Our studies focussed on preparing therapeutic
vaccines with low-cost technologies by
DNA preparation fused to either plant-virus or plant-toxin genes, such as
saporin, and by plant-produced
antigens. In particular, plant-derived
antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in
vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic
transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause
cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for
immunotherapies with genetic or plant-derived therapeutic
vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune
therapy that seems to be very effective in patients.