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 language | English (US) |
|---|---|
| Pages (from-to) | 873-885 |
| Number of pages | 13 |
| Journal | Cancer Gene Therapy |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 27 2006 |
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Keywords
- Alphavirus replicon
- Angiogenesis
- Cancer vaccine
- Human papillomavirus
- Immunotherapy
- T-cell immunity
ASJC Scopus subject areas
- Cancer Research
- Genetics
Cite this
Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity. / Cheng, W. F.; Lee, C. N.; Su, Y. N.; Chai, C. Y.; Chang, M. C.; Polo, J. M.; Hung, Chien-Fu; Wu, Tzyy Choou; Hsieh, C. Y.; Chen, C. A.
In: Cancer Gene Therapy, Vol. 13, No. 9, 27.09.2006, p. 873-885.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity
AU - Cheng, W. F.
AU - Lee, C. N.
AU - Su, Y. N.
AU - Chai, C. Y.
AU - Chang, M. C.
AU - Polo, J. M.
AU - Hung, Chien-Fu
AU - Wu, Tzyy Choou
AU - Hsieh, C. Y.
AU - Chen, C. A.
PY - 2006/9/27
Y1 - 2006/9/27
N2 - 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.
AB - 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.
KW - Alphavirus replicon
KW - Angiogenesis
KW - Cancer vaccine
KW - Human papillomavirus
KW - Immunotherapy
KW - T-cell immunity
UR - http://www.scopus.com/inward/record.url?scp=33747280364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747280364&partnerID=8YFLogxK
U2 - 10.1038/sj.cgt.7700956
DO - 10.1038/sj.cgt.7700956
M3 - Article
C2 - 16645621
AN - SCOPUS:33747280364
VL - 13
SP - 873
EP - 885
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 9
ER -