Recombinant lipidated hpv e7 induces a th-1-biased immune response and protective immunity against cervical cancer in a mouse model
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Authors
Huang, Chiung-Yi
Chen, Jeremy J. W.
Shen, Kuan-Yin
Chang, Li-Sheng
Yeh, Yi-Chen
Chen, I-Hua
Chong, Pele
Liu, Shih-Jen
Leng, Chih-Hsiang
Issue Date
2012-07-18
Type
Article
Language
en_US
Keywords
Recombinant Lipidated HPV E7 , Th-1-Biased Immune Response , Protective Immunity , Cervical Cancer
Alternative Title
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 cm3 on day 40, whereas the tumor volume in mice treated with rE7m was 2.28±1.21 cm3. The tumor volume of the entire control group was over 3 cm3. 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.
Description
Citation
Huang, C. Y., Chen, J. J., Shen, K. Y., Chang, L. S., Yeh, Y. C., Chen, I. H., Chong, P., Liu, S. J., & Leng, C. H. (2012). Recombinant lipidated HPV E7 induces a Th-1-biased immune response and protective immunity against cervical cancer in a mouse model. PloS one, 7(7), e40970. https://doi.org/10.1371/journal.pone.0040970
Publisher
PloS One