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- Title
Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.
- Authors
Cheng, W-F; Lee, C-N; Su, Y-N; Chai, C-Y; Chang, M-C; Polo, J M; Hung, C-F; Wu, T-C; Hsieh, C-Y; Chen, C-A
- 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.Cancer Gene Therapy (2006) 13, 873–885. doi:10.1038/sj.cgt.7700956; published online 28 April 2006
- Subjects
CALRETICULIN; CALCIUM-binding proteins; TUMOR antigens; CANCER vaccines; GENE therapy
- Publication
Cancer Gene Therapy, 2006, Vol 13, Issue 9, p873
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700956