title: [Development of new therapies targeting human papillomavirus molecules].
abstract: High-risk HPV E6 and E7 oncogenes are an ideal targeting gene for treatment of cervical cancer. In this paper, we introduce researches on cancer-immunotherapy targeting HPV E7 through mucosal immunity and E6/E7-targeting siRNA therapy using PEGylated polymeric micelles. Therapeutic HPV vaccine has also attracted attention as a cancer immunotherapy agent. We have found homing of Integrin β7-positive intestinal mucosal lymphocyte on the cervical mucosa. In this study, we generated a novel therapeutic vaccine; an HPV E7-expressing Lactobacillus casei (LacE7) to induce anti-HPV cellular immunity directly to intestinal mucosa. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were counted E7 specific INFγ-producing cells (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. We confirmed induction of anti-E7 IFNγ-producing cells in the cervix lymphocytes obtained from these patients. E6/E7 siRNA therapy requires a delivery system for its systemic intravenous administration. We here demonstrated that intravenous injection of HPV16 or 18 E6/E7 siRNA polymeric micelles suppressed excellently an increase in size of subcutaneous tumor formed by SiHa or HeLa cell, respectively. Our drug-delivery technology using polymeric micelles enabled the successful systemic administration of siRNA to exhibit anti-tumor effect.
authors.affiliation: Associate Professor Department of Obstetrics and Gynecology, Graduate School of Medicine.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology; D002584:Cervix Uteri; D016503:Drug Delivery Systems; D055808:Drug Discovery / Q000639:trends; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007167:Immunotherapy; D039641:Integrin beta Chains; D007371:Interferon-gamma; D007780:Lacticaseibacillus casei; D008297:Male; D008823:Micelles; D058990:Molecular Targeted Therapy; D009092:Mucous Membrane / Q000166:cytology; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000627:therapeutic use; D011108:Polymers; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000821:virology*
chemical_list: D039641:Integrin beta Chains; D008823:Micelles; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011108:Polymers; D034741:RNA, Small Interfering; C091368:integrin beta7; D007371:Interferon-gamma