title: Vaccination with OK-432 followed by TC-1 tumor lysate leads to significant antitumor effects.
abstract: Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4(+) T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4(+) T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Chen
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Yen
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Chyi-Long
authors.initials: CL
authors.lastname: Lee
authors.forename: Yung-Kuei
authors.initials: YK
authors.lastname: Soong
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Lin
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010844:Picibanil / Q000276:immunology / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
chemical_list: D050725:Papillomavirus E7 Proteins; D014765:Viral Vaccines; D010844:Picibanil