Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis.
Antigen-specific cancer immunotherapy and antiangiogenesis are feasible strategies for cancer therapy because they can potentially treat systemic tumors at multiple sites in the body while discriminating between neoplastic and non-neoplastic cells. We have previously developed a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus-16 E7 and have found that this vaccine generates strong E7-specific antitumor immunity and antiangiogenic effects in vaccinated mice. In this study, we characterized the domains of CRT to produce E7-specific antitumor immunity and antiangiogenic effects by generating DNA vaccines encoding each of the three domains of CRT (N, P, and C domains) linked to the HPV-16 E7 antigen. We found that C57BL/6 mice vaccinated intradermally with DNA encoding the N domain of CRT (NCRT), the P domain of CRT (PCRT), or the C domain of CRT (CCRT) linked with E7 exhibited significant increases in E7-specific CD8(+) T cell precursors and impressive antitumor effects against E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. In addition, the N domain of CRT also showed antiangiogenic properties that might have contributed to the antitumor effect of NCRT/E7. Thus, the N domain of CRT can be linked to a tumor antigen in a DNA vaccine to generate both antigen-specific immunity and antiangiogenic effects for cancer therapy.
Cheng
Wen-Fang
WF
Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
Hung
Chien-Fu
CF
Chen
Chi-An
CA
Lee
Chien-Nan
CN
Su
Yi-Ning
YN
Chai
Chee-Yin
CY
Boyd
David A K
DA
Hsieh
Chang-Yao
CY
Wu
T-C
TC
D020533:Angiogenesis Inhibitors; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D037282:Calreticulin / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002461:Cell Line, Transformed; D008175:Lung Neoplasms / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D017434:Protein Structure, Tertiary; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic
D020533:Angiogenesis Inhibitors; D037282:Calreticulin; D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16