WEN-FANG CHENGCHIEN-NAN LEESu Y.-N.Chai C.-Y.Chang M.-C.Polo J.M.Hung C.-F.Wu T.-C.CHANG-YAO HSIEHCHI-AN CHEN2020-02-142020-02-1420060929-19032-s2.0-33747280364https://scholars.lib.ntu.edu.tw/handle/123456789/458654Alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. In this study, we used the replication-defective vaccine vector SIN replicon particles from a new packaging cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT) linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein. The linkage of CRT to E7 in SIN replicon particles resulted in a significant increase in E7-specific CD8+ T-cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon particles enhanced presentation of E7 through the major histocompatibility complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons. Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon particles also generated significant reduction of lung tumor nodules, suggesting that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7 replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long-term in vivo tumor protection effects and antigen-specific memory immunities. We concluded that the CRT strategy used in the context of SIN replicon particles facilitated the generation of a highly effective vaccine for cancer prophylaxis and immunotherapy. ? 2006 Nature Publishing Group All rights reserved.[SDGs]SDG3calreticulin; cancer vaccine; major histocompatibility antigen class 1; protein E7; tumor antigen; virus vector; Alpha virus; angiogenesis; animal cell; animal experiment; antigen specificity; antineoplastic activity; article; cancer immunotherapy; cell lysate; cellular immunity; controlled study; dendritic cell; female; Human papillomavirus type 16; immunological memory; memory cell; nonhuman; priority journal; replicon; Sindbis virus; T lymphocyte activation; tumor immunity; virus particle; Analysis of Variance; Animals; Calreticulin; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Gene Therapy; Human papillomavirus 16; Humans; Immunologic Memory; Immunotherapy; Lung Neoplasms; Mice; Mice, Inbred C57BL; Papillomavirus E7 Proteins; Replicon; Sindbis Virus; Alphavirus; Human papillomavirus type 16; Sindbis virusjournal article10.1038/sj.cgt.770095656601533000