Journal
JOURNAL OF MICROBIOLOGY
Volume 46, Issue 6, Pages 728-736Publisher
MICROBIOLOGICAL SOCIETY KOREA
DOI: 10.1007/s12275-008-0087-1
Keywords
cervical cancer; human papillomavirus 16 (HPV16); cytotoxic T-lymphocyte antigen 4 (CTLA4); vaccine
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Funding
- Graduate School at Shenzhen, Tsinghua University
- Shenzhen Citizen Hospital, Shenzhen
- Shenzhen National Key Lab of Health Science and Technology
- Key Lab of Gene & Antibody Therapy
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Cervical cancer is caused by infection by high-risk human papillomavirus (HPV), especially HPV16. Limitations in current treatments of cervical cancers call for the development of new and improved immunotherapies. This study aims at investigating the efficacy of a novel vaccine consisting of modified HPV 16E7 fused with human cytotoxic T-lymphocyte antigen 4 (CTLA4). The regions in HPV16 E7 gene associated with its transformation and CTL-enhanced response were modified; the resultant HPV16mE7 was fused with extracellular region of CTLA4 to generate HPVml6E7-eCTLA4 fusion protein. Binding of this fusion protein to B7 molecules expressed on antigen presenting-cells (APCs) was demonstrated. C57BL/6 (H-2(b)) mice immunized with low dose of the fusion protein (10 mu g) produced higher titer antibody and stronger specific CTL response, and expressed higher levels of IFN-gamma and IL-12, compared with those immunized with HPVml6E7 only or admixture of HPVml6E7 and CTLA4, or PBS; and were protected from lethal dose tumor challenge. Tumor growth was retarded and survival prolonged in mouse models with the fusion protein treatment. Our results demonstrate that fusion of HPV16 E7 with eCTLA4 targeting APCs resulted in enhanced immunity, and that this fusion protein may be useful for improving the efficacy of immunotherapeutic treatments of cervical cancer and other HPV16 infection-associated tumors.
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