title: Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.
abstract: A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.
authors: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: W-F
authors: WF
authors: Cheng
authors: M-C
authors: MC
authors: Chang
authors: W-Z
authors: WZ
authors: Sun
authors: C-N
authors: CN
authors: Lee
authors: H-W
authors: HW
authors: Lin
authors: Y-N
authors: YN
authors: Su
authors: C-Y
authors: CY
authors: Hsieh
authors: C-A
authors: CA
authors: Chen
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D055513:Connective Tissue Growth Factor; D003713:Dendritic Cells / Q000276:immunology; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016233:Immunotherapy, Active / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D023041:Xenograft Model Antitumor Assays
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D019496:Cancer Vaccines; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D055513:Connective Tissue Growth Factor