Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity

W. F. Cheng, C. N. Lee, Y. N. Su, C. Y. Chai, M. C. Chang, J. M. Polo, C. F. Hung, T. C. Wu, C. Y. Hsieh, C. A. Chen

Research output: Contribution to journalArticle

Abstract

Alphavirus 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.

Original languageEnglish (US)
Pages (from-to)873-885
Number of pages13
JournalCancer Gene Therapy
Volume13
Issue number9
DOIs
StatePublished - Sep 27 2006

Keywords

  • Alphavirus replicon
  • Angiogenesis
  • Cancer vaccine
  • Human papillomavirus
  • Immunotherapy
  • T-cell immunity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity'. Together they form a unique fingerprint.

  • Cite this