The Micro-Immunotherapy Medicine 2LPAPI? Displays Immune-Modulatory Effects in a Model of Human Papillomavirus Type-16 L1-Protein Capsid-Treated Human Peripheral Blood Mononuclear Cells and Antiproliferative Effects in a Model of Cervical Cancer Cells

The human papillomavirus (HPV), a major carcinogenic pathogen, can cause cervical cancer through persistent infection. The immune system typically fights off the virus, albeit long-term activation may promote carcinogenesis. The micro-immunotherapy medicine 2LPAPI (R) holds promise for aiding viral clearance and mitigating cervical cancer risk, and our research aimed to examine the effects of this medicine in vitro. We focused our investigations on the two most prevalent genotypes of HPV causing persistent infection, HPV-16 and HPV-18. We found that 2LPAPI (R) boosted the secretion of IL-6, IFN-gamma, and IP-10 in human immune cells when exposed to HPV-16 proteins, suggesting enhanced defensive responses to HPV-16. Some of the active substances curtailed T-cell proliferation and activity and displayed antiproliferative properties on HPV-18 positive cervical cancer-derived HeLa cells in nutrient-restricted conditions. These results unveil 2LPAPI (R)'s potential dual role: immunomodulation for HPV-16-affected immune cells and antiproliferative activity against a model of HPV-18-positive-cervical cancer cells. Human papillomavirus (HPV) is the second most common infectious agent causing cancer. Persistent infection with high-risk (HR)-HPV can lead to cervical intra-epithelial neoplasia and cervical carcinomas (CC). While host immune response is necessary for viral clearance, chronic immune activation contributes to a low-grade inflammation that can ultimately lead to carcinogenesis. The micro-immunotherapy medicine (MIM) 2LPAPI (R) could be a valuable tool to manage the clearance of the virus and reduce the risk of developing CC. In this in vitro study, we aimed to investigate its mode of action. We showed that actives from the MIM increased the IL-6, IFN-gamma, and IP-10 secretion in human peripheral blood mononuclear cells (PBMCs) exposed to peptides derived from the HPV-16 capsid (HPV16((L1))). This could reflect an increase in the immune activity toward HPV-16. At the same time, some active substances reduced the lympho-proliferation and the expression of T-cell activation markers. Finally, some of the MIM actives displayed antiproliferative effects in CC-derived HeLa cells under serum-starvation conditions. Altogether, this body of data highlighted for the first time the dual effect of MIM in the framework of HR-HPV infections as a potential (i) immune modulator of HPV16((L1))-treated PBMCs and (ii) antiproliferative agent of HPV-positive CC cells.