Each has been interrogated in a series of preclinical studies and in Phase I/II clinical studies in the CCR as well as by other inves tigators. Preclinical studies and early clinical studies are demonstrating the relative lack of additional toxicities with enhanced clinical benefit employing combinations of 2 of these agents. Preclinical studies are now demonstrating that the combined use of agents from each of the immune -mediating categories described above elicits the most immune -mediated anti -tumor activities. 1.2.2.1 HPV Vaccine PDS0101 is a novel nanoparticle -based immunotherapy (therapeutic vaccine) developed to treat genital cancers such as anal, cervical, vulvar cancer etc. and their precancers (late -stage dysplasia/neoplasia), as well as head and neck cancers caused by infect ion with the human papilloma virus (HPV). PDS0101 is a subcutaneously administered therapy consisting of two vialed components mixed by the investigator at the time of administration. The immunotherapy is composed of liposomal nanoparticles of the pure immunologically active R enantiomer of the 11 Abbreviated Title: Combo Immunotx in HPV Cancers Version Date: 05.12.2023 cationic (positively charged) lipid DOTAP (dioleoyl -trimethylammonium propane) mixed with 6 lipidated antigenic peptides derived from the HPV-16 E6 and E7 proteins. In-vivo and in-vitro studies performed in normal and transgenic mouse models as well as in-vitro studies using human lymphocytes in culture demonstrated potent immune modulating effects by R-DOTAP. The pure R stereoisomer of DOTAP acts as a potent activator of the MAP kinase signaling pathway leading to activation and maturation of dendritic cells and subsequent induction of the production and release of cytokines and chemokines critical for promotion of an effective immune response. The positive charge on the surface of R -DOTAP liposomes facilitates their uptake by the dendritic cell. This in turn facilitates uptake of the HPV peptide antigen micelles and the antigenic processing and presen tation by dendritic cells to T -cells. The ability of cationic liposomes to destabilize endosomes facilitates antigen delivery into the cytoplasm of the dendritic cells and other antigen presenting cells [13]. Effective induction of cytotoxic T -lymphoc yte (CTL) responses and tumor regression has been demonstrated in the pre- clinical studies.