Comparison of HPV DNA vaccines employing intracellular targeting strategies

J. W. Kim, C. F. Hung, J. Juang, T. He, Tae Woo Kim, D. K. Armstrong, S. I. Pai, P. J. Chen, C. T. Lin, D. A. Boyd, T. C. Wu

Research output: Contribution to journalArticle

97 Citations (Scopus)

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 languageEnglish
Pages (from-to)1011-1018
Number of pages8
JournalGene Therapy
Volume11
Issue number12
DOIs
Publication statusPublished - 2004 Jun 1
Externally publishedYes

Fingerprint

Papillomavirus Vaccines
DNA Vaccines
Calreticulin
T-Lymphocytes
Vaccination
Antigen Presentation
Firearms
Antigens
Lysosome-Associated Membrane Glycoproteins
Neoplasms
HSP70 Heat-Shock Proteins
Human papillomavirus 16
Langerhans Cells
Infection Control
Mycobacterium tuberculosis
Uterine Cervical Neoplasms
Genes
Down-Regulation
Clinical Trials

Keywords

  • DNA vaccines
  • E7
  • Human papillomavirus (HPV)
  • Immunotherapy

ASJC Scopus subject areas

  • Genetics

Cite this

Kim, J. W., Hung, C. F., Juang, J., He, T., Kim, T. W., Armstrong, D. K., ... Wu, T. C. (2004). Comparison of HPV DNA vaccines employing intracellular targeting strategies. Gene Therapy, 11(12), 1011-1018. https://doi.org/10.1038/sj.gt.3302252

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 journalArticle

Kim, JW, Hung, CF, Juang, J, He, T, Kim, TW, Armstrong, DK, Pai, SI, Chen, PJ, Lin, CT, Boyd, DA & Wu, TC 2004, 'Comparison of HPV DNA vaccines employing intracellular targeting strategies', Gene Therapy, vol. 11, no. 12, pp. 1011-1018. https://doi.org/10.1038/sj.gt.3302252
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. / Comparison of HPV DNA vaccines employing intracellular targeting strategies. In: Gene Therapy. 2004 ; Vol. 11, No. 12. pp. 1011-1018.
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