Abstract LB182: Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor

Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. 6 major histocompatibility complex (MHC) class I (MHC-I) epitopes were predicted to be immunogenic by sequencing a murine cell line that expresses E6/E7. A liposomal vaccine made of cobalt-porphyrin-phospholipid (CoPoP) and synthetic 9-mer epitopes appended with 3 histidine residues, resulting in rapid formation of stable peptide-liposome particles. Immunization with these predicted 6 peptides led to protection from tumor challenge on mice. Of the 6 peptides screened, only the previously identified E749-57 epitope has anti-tumor efficacy. The peptide-liposome particles that formed upon mixing E7HHH49-57 with CoPoP liposomes were stable in serum and avidly taken up by immune cells in vitro and rapidly released in lysosome. As a prophylactic vaccine, liposomal E7HHH49-57 vaccine protected mice from tumor challenge and re-challenge. As a therapeutic vaccine, immunization with the synthetic short peptide at a dose of 100 ng protected mice when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses were ineffective with the Poly(I:C) adjuvant. CoPoP induced strong infiltrating CD8+ T response within the tumor microenvironment with improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reversed the growth of large established tumors, permanently eradicating subcutaneous tumors upwards of 100 mm3, and also completely eradicated lung tumors in a metastasis model. Citation Format: Xuedan He, Shiqi Zhou, Breandan Quinn, Dushyant Jahagirdar, Joaquin Ortega, Scott I. Abrams, Jonathan F. Lovell. Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB182.