Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.
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.
Cheng
W-F
WF
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chang
M-C
MC
Sun
W-Z
WZ
Lee
C-N
CN
Lin
H-W
HW
Su
Y-N
YN
Hsieh
C-Y
CY
Chen
C-A
CA
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
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