title: Recombinant lipidated HPV E7 induces a Th-1-biased immune response and protective immunity against cervical cancer in a mouse model.
abstract: The E7 oncoprotein of human papillomavirus (HPV) is an ideal target for developing immunotherapeutic strategies against HPV-associated tumors. However, because protein-based immunogens alone are poor elicitors of the cytotoxic T-lymphocyte (CTL) responses, they have been difficult to exploit for therapeutic purposes. In this study, we report that a recombinant lipoprotein consisting of inactive E7 (E7m) biologically linked to a bacterial lipid moiety (rlipo-E7m) induces the maturation of mouse bone marrow-derived dendritic cells through toll-like receptor 2 (TLR2), skews the immune responses toward the Th1 responses and induces E7-specific CTL responses. We further studied the ability of rlipo-E7m to provide protection against a TC-1 tumor cell challenge in an animal model. Mice prophylactically immunized with two 10-µg doses of rlipo-E7m were found to be free of TC-1 tumor growth. Experiments in a therapeutic immunization model showed that the tumor volume in mice receiving a single dose of rlipo-E7m was less than 0.01 cm(3) on day 40, whereas the tumor volume in mice treated with rE7m was 2.28±1.21 cm(3). The tumor volume of the entire control group was over 3 cm(3). In addition, we demonstrated that the CD8+ T cells play a major role in anti-tumor immunity when administration of rlipo-E7m. These results demonstrate that rlipo-E7m could be a promising candidate for treating HPV-associated tumors.
authors: National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli, Taiwan, Republic of China.
authors: Chiung-Yi
authors: CY
authors: Huang
authors: Jeremy J W
authors: JJ
authors: Chen
authors: Kuan-Yin
authors: KY
authors: Shen
authors: Li-Sheng
authors: LS
authors: Chang
authors: Yi-Chen
authors: YC
authors: Yeh
authors: I-Hua
authors: IH
authors: Chen
authors: Pele
authors: P
authors: Chong
authors: Shih-Jen
authors: SJ
authors: Liu
authors: Chih-Hsiang
authors: CH
authors: Leng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D007107:Immune System; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027383:Papillomaviridae / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000821:virology; D018417:Th1 Cells / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D008055:Lipids; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins