Immunological Protection against HPV16 E7-Expressing Human Esophageal Cancer Cell Challenge by a Novel HPV16-E6/E7 Fusion Protein Based-Vaccine in a Hu-PBL-SCID Mouse Model(Biopharmacy)
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概要
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Increasing evidence has suggested that infection with high-risk human papillomavirus (HPVs) is closely associated with esophageal squamous cell carcinoma (ESCC) in China. The E6 and E7 oncoproteins expressed in ESCC are considered as attractive tumor-specific antigen targets for immunotherapy. We have reported that the HPV16 mE6Δ/mE7/TBhsp70Δ fusion protein vaccination induced powerful anti-tumor immunity against TC-1 tumor cells in a C57BL/6 mouse model. In the present study, we further evaluate the protective efficacy of this fusion protein vaccine using an HPV E7-expressing human ESCC cell line (EC9706) and a Hu-PBL-SCID mouse model. We demonstrated that immunization with the fusion protein vaccine caused significant inhibition of tumor growth with the delay time to tumor detection (tests vs. controls, 16d vs. 9d, p<0.01) and much smaller tumor size (p<0.01) in vivo. The inhibitory rate was ca. 69.6%, and 25% of the fusion protein vaccinated-mice remained tumor free by the end of the experiment (42d). Furthermore, the activated lymphocytes (CD8^+) were capable of infiltrating into the tumor site, and much more apoptotic cells along with activation of caspase-3 were observed in the tumors from vaccinated-mice. Also, high expression levels of human IFN-γ, TNF-α, granzyme B and perforin were detected in the tumors from vaccinated-mice. Therefore, we concluded that the HPV16 mE6Δ/mE7/TBhsp70Δ fusion protein vaccine is able to stimulate cellular-mediated immune response against E7-containing ESCC cells through CD8^+-dependent CTL-induced apoptosis in Hu-PBL-SCID mice. These findings provide a scientific basis for HPV E7-expressing ESCC active immunotherapy.
- 公益社団法人日本薬学会の論文
- 2007-01-01
著者
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Liu Bo
Department Of Cellular And Molecular Biology Cancer Institute Of Hospital Peking Union Medical Colle
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LIU Bo
Laboratory of Nanotechnology, Shanghai Institute of Microsystem and Information Technology, Chinese
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Liu Qiao
Laboratory Of Cellular And Molecular Biology
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Zhao Qingzheng
Department Of Cellular And Molecular Biology Cancer Institute Of Hospital Peking Union Medical Colle
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LU Yuanzhi
Laboratory of Cellular and Molecular Biology
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ZHANG Zhixin
Beijing Blood Center
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SONG Xinxin
Laboratory of Cellular and Molecular Biology
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WANG Mingrong
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Peking Union Medical Colleg
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ZHAO Xinhua
Laboratory of Cellular and Molecular Biology
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ZHAO Qingzheng
Laboratory of Cellular and Molecular Biology
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Song Xinxin
Department Of Cellular And Molecular Biology Cancer Institute Of Hospital Peking Union Medical Colle
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Zhao Xinhua
Department Of Cellular And Molecular Biology Cancer Institute Of Hospital Peking Union Medical Colle
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Zhang Zhixin
Department Of Oral And Maxillofacial Surgery Ninth People's Hospital School Of Medicine Shangha
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Wang Mingrong
State Key Laboratory Of Molecular Oncology Cancer Institute & Hospital Peking Union Medical Coll
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Liu Bo
Laboratory Of Biomechanics School Of Medicine Shanghai Jiao Tong University
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