title: A synthetic chimeric peptide harboring human papillomavirus 16 cytotoxic T lymphocyte epitopes shows therapeutic potential in a murine model of cervical cancer.
abstract: Infection with human papillomavirus (HPV) such as HPV16 is known to be associated with cervical cancer. The E6 and E7 oncoproteins of this virus are attractive targets for T-cell-based immunotherapy to cervical cancer. In our study, software predicted, multiple H-2D(b) restricted HPV16 cytotoxic T lymphocytes (CTL) epitopes on a synthetic chimeric peptide, was used along with different immunopotentiating adjuvants such as alum, heat-killed Mycobacterium w (Mw) cells, and poly D,L-lactic-co-glycolide (PLGA) microspheres. We have shown that subcutaneous immunization with H-2D(b)-restricted HPV16 peptide was able to generate CTL-mediated cytolysis of HPV16 E6- and E7-expressing TC-1 tumor cells in vitro, as well as protect against in vivo challenge with TC-1 cells in C57BL/6 mice. In vitro, this chimeric peptide showed best efficacy with PLGA microspheres, moderate with alum, and least with Mw as adjuvant. This approach may thus provide a potential peptide-based therapeutic candidate vaccine for the control of HPV infection and hence cervical cancer.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Chandresh
authors.initials: C
authors.lastname: Sharma
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
authors.forename: Teena
authors.initials: T
authors.lastname: Mohan
authors.forename: Jatin
authors.initials: J
authors.lastname: Shrinet
authors.forename: N
authors.initials: N
authors.lastname: Latha
authors.forename: Neeta
authors.initials: N
authors.lastname: Singh
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012097:Repressor Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D014765:Viral Vaccines / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16