Enchancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death

Tae Woo Kim, C. F. Hung, J. Juang, L. He, J. M. Hardwick, T. C. Wu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

DNA-based alphaviral RNA replicon vectors, also called suicidal DNA vectors, alleviate the concerns of integration or transformation related to conventional DNA vectors since suicidal DNA vectors eventually cause apoptosis of transfected cells. However, the expression of inserted genes in these vectors is transient and the potency of suicidal DNA vaccines may be compromised because of apoptotic cell death. Therefore, to enhance the immune response to the human papillomavirus type 16 (HPV-16) E7 antigen, we generated a DNA -based Semliki Forest virus vector, pSCA1, encoding E7 fused with BCL-xL, an antiapoptotic member of the BCL-2 family. Our results indicated that pSCA1 encoding E7/BCL-xL fusion protein delayed cell death in the pSCA1-transfected dendritic cell line and generated significantly higher E7-specific CD8+ T-cell-mediated immune responses and better antitumor effects than pSCA1 encoding wild-type E7 gene in vaccinated mice. The antiapoptotic function of BCL-xL is important for the enhancement of antigen-specific CD8+ T-cell responses in vaccinated mice, because a point mutant of BCL-xL lacking antiapoptotic function was ineffective. These results suggest that strategies to delay suicidal DNA-induced cell death using antiapoptotic proteins may greatly enhance the potency of suicidal DNA.

Original languageEnglish
Pages (from-to)336-342
Number of pages7
JournalGene Therapy
Volume11
Issue number3
DOIs
Publication statusPublished - 2004 Feb 1
Externally publishedYes

Fingerprint

Vaccine Potency
DNA Vaccines
Cell Death
DNA
Semliki forest virus
CD8 Antigens
T-Lymphocytes
Replicon
Human papillomavirus 16
Dendritic Cells
Proteins
RNA
Apoptosis
Gene Expression
Antigens
Cell Line

Keywords

  • Antiapoptosis
  • Human papillomavirus
  • Immunotherapy
  • Suicidal DNA
  • Vaccines

ASJC Scopus subject areas

  • Genetics

Cite this

Enchancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death. / Kim, Tae Woo; Hung, C. F.; Juang, J.; He, L.; Hardwick, J. M.; Wu, T. C.

In: Gene Therapy, Vol. 11, No. 3, 01.02.2004, p. 336-342.

Research output: Contribution to journalArticle

Kim, Tae Woo ; Hung, C. F. ; Juang, J. ; He, L. ; Hardwick, J. M. ; Wu, T. C. / Enchancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death. In: Gene Therapy. 2004 ; Vol. 11, No. 3. pp. 336-342.
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