Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism

WEN-FANG CHENGChang M.-C.WEI-ZEN SUNCHIEN-NAN LEELin H.-W.Su Y.-N.CHANG-YAO HSIEHCHI-AN CHEN2020-01-222020-01-222008https://scholars.lib.ntu.edu.tw/handle/123456789/452770A 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. ? 2008 Nature Publishing Group All rights reserved.[SDGs]SDG3connective tissue growth factor; DNA vaccine; protein E7; tumor antigen; animal cell; animal experiment; animal model; apoptosis; article; cancer immunotherapy; cancer prevention; CD4+ T lymphocyte; CD8+ T lymphocyte; cell survival; controlled study; dendritic cell; drug potency; female; Human papillomavirus type 16; immune response; lymph node; malignant neoplastic disease; mouse; nonhuman; nonviral gene delivery system; priority journal; vaccination; wild type; Animals; Antigen Presentation; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Survival; Dendritic Cells; Gene Therapy; Genetic Engineering; Humans; Immediate-Early Proteins; Immunotherapy, Active; Intercellular Signaling Peptides and Proteins; Mice; Neoplasms; Oncogene Proteins, Viral; Xenograft Model Antitumor Assays; Human papillomavirus; MusConnective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanismjournal article10.1038/gt.2008.252-s2.0-45749116580