Oncotarget

Research Papers:

Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer

Chao-Chih Wu, Fang-Cih Wu, Yun-Tin Hsu, Yu-Chia Hsiao, Yuh-Cheng Yang, C. Allen Chang and Chih-Long Chang _

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Oncotarget. 2017; 8:33024-33036. https://doi.org/10.18632/oncotarget.16032

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Abstract

Chao-Chih Wu2, Fang-Cih Wu2,4, Yun-Tin Hsu2, Yu-Chia Hsiao2, Yuh-Cheng Yang1, C. Allen Chang4,5, Chih-Long Chang1,2,3

1Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City, Taiwan

2Departmental of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan

3Department of Medicine, Mackay Medical College, Sanchi, New Taipei City, Taiwan

4Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei City, Taiwan

5Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei City, Taiwan

Correspondence to:

Chih-Long Chang, email: clchang@mmc.edu.tw

C. Allen Chang, email: cachang@ym.edu.tw

Keywords: DNA vaccine, BAFF

Received: January 02, 2017    Accepted: February 13, 2017    Published: March 09, 2017

ABSTRACT

B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)–Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects. We found that this vaccine increased E7-specific CD8+ T-cell immune responses, engendered major antitumor effects against E7-expressing tumors, and prolonged the survival of the immunized mice. Interestingly, vaccinating B-cell-deficient mice with BAFF–E7 revealed considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do not contribute to this immune response. Image analysis through confocal fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to the ER, but not BAFF lacking 128 N-terminal residues that generated a lower number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated that the ER-targeting characteristic of BAFF is the main factor improving the potency of DNA vaccines.


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