Abstract
Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dll) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8+ T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8+ T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions.
| Original language | English |
|---|---|
| Pages (from-to) | 1011-1018 |
| Number of pages | 8 |
| Journal | Gene Therapy |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2004 Jun 1 |
| Externally published | Yes |
Fingerprint
Keywords
- DNA vaccines
- E7
- Human papillomavirus (HPV)
- Immunotherapy
ASJC Scopus subject areas
- Genetics
Cite this
Comparison of HPV DNA vaccines employing intracellular targeting strategies. / Kim, J. W.; Hung, C. F.; Juang, J.; He, T.; Kim, Tae Woo; Armstrong, D. K.; Pai, S. I.; Chen, P. J.; Lin, C. T.; Boyd, D. A.; Wu, T. C.
In: Gene Therapy, Vol. 11, No. 12, 01.06.2004, p. 1011-1018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of HPV DNA vaccines employing intracellular targeting strategies
AU - Kim, J. W.
AU - Hung, C. F.
AU - Juang, J.
AU - He, T.
AU - Kim, Tae Woo
AU - Armstrong, D. K.
AU - Pai, S. I.
AU - Chen, P. J.
AU - Lin, C. T.
AU - Boyd, D. A.
AU - Wu, T. C.
PY - 2004/6/1
Y1 - 2004/6/1
N2 - Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dll) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8+ T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8+ T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions.
AB - Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dll) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8+ T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8+ T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions.
KW - DNA vaccines
KW - E7
KW - Human papillomavirus (HPV)
KW - Immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=3142704466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3142704466&partnerID=8YFLogxK
U2 - 10.1038/sj.gt.3302252
DO - 10.1038/sj.gt.3302252
M3 - Article
VL - 11
SP - 1011
EP - 1018
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 12
ER -