Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

WEN-FANG CHENGHung C.-F.CHI-AN CHENCHIEN-NAN LEESu Y.-N.Chai C.-Y.Boyd D.A.K.CHANG-YAO HSIEHWu T.-C.2020-02-142020-02-1420050264-410X2-s2.0-18944376330https://scholars.lib.ntu.edu.tw/handle/123456789/458665Antigen-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. ? 2004 Published by Elsevier Ltd.[SDGs]SDG3calreticulin; DNA vaccine; amino terminal sequence; animal experiment; animal tissue; antiangiogenic activity; article; carboxy terminal sequence; controlled study; mouse; nonhuman; pineapple; priority journal; protein domain; T lymphocyte; tumor immunity; Angiogenesis Inhibitors; Animals; Calreticulin; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Transformed; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Oncogene Proteins, Viral; Protein Structure, Tertiary; Vaccines, DNA; Vaccines, SyntheticCharacterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesisjournal article10.1016/j.vaccine.2004.10.03256601533000