HPV-Associated Tumor Eradication by Vaccination with Synthetic Short Peptides and Particle-Forming Liposomes.
Xuedan HeShiqi ZhouBreandan QuinnDushyant JahagirdarJoaquin OrtegaScott I AbramsJonathan F LovellPublished in: Small (Weinheim an der Bergstrasse, Germany) (2021)
Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. Using a murine cell line that expresses these, the genes are sequenced, and six predicted major histocompatibility complex (MHC) class I (MHC-I) epitopes are identified. A liposomal vaccine adjuvant based on cobalt-porphyrin-phospholipid (CoPoP) is admixed with synthetic 9-mer epitopes appended with three histidine residues, resulting in rapid formation of peptide-liposome particles. Immunization with multivalent peptides leads to protection from tumor challenge. Of the peptides screened, only the previously identified E749-57 epitope is functional. The peptide-liposome particles that form upon mixing E7HHH49-57 with CoPoP liposomes are stable in serum and are avidly taken up by immune cells in vitro. Immunization results in robust protection from tumor challenge and re-challenge. A 100 ng peptide dose protects mice in a therapeutic tumor challenge when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses are ineffective with the polyinosinic-polycytidylic (poly(I:C)) adjuvant. CoPoP induces a strong infiltrating CD8+ T-cell response within the tumor microenvironment with an improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reverses the growth of large established tumors, eradicating subcutaneous tumors upwards of 100 mm3 . Immunization also eradicates lung tumors in a metastasis model.
Keyphrases
- drug delivery
- early stage
- endothelial cells
- drug release
- gene expression
- photodynamic therapy
- amino acid
- high grade
- randomized controlled trial
- transcription factor
- skeletal muscle
- adipose tissue
- fatty acid
- helicobacter pylori
- combination therapy
- metal organic framework
- reduced graphene oxide
- sensitive detection
- pluripotent stem cells