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Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer.
Wu, Chao-Chih; Wu, Fang-Cih; Hsu, Yun-Tin; Hsiao, Yu-Chia; Yang, Yuh-Cheng; Chang, C Allen; Chang, Chih-Long.
Afiliación
  • Wu CC; Departmental of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • Wu FC; Departmental of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • Hsu YT; Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei City, Taiwan.
  • Hsiao YC; Departmental of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • Yang YC; Departmental of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • Chang CA; Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City, Taiwan.
  • Chang CL; Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei City, Taiwan.
Oncotarget ; 8(20): 33024-33036, 2017 May 16.
Article en En | MEDLINE | ID: mdl-28423693
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Vacunas contra el Cáncer / Vacunas de ADN / Infecciones por Papillomavirus / Proteínas E7 de Papillomavirus / Factor Activador de Células B / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Vacunas contra el Cáncer / Vacunas de ADN / Infecciones por Papillomavirus / Proteínas E7 de Papillomavirus / Factor Activador de Células B / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos