A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication

Rong Xiang, Noriko Mizutani, Yunping Luo, Claudia Chiodoni, He Zhou, Masato Mizutani, Yi Ba, Juergen C. Becker, Ralph A. Reisfeld

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

A novel strategy achieved the eradication of lung tumor metastases by joint suppression of angiogenesis in the tumor neovasculature and induction of tumor cell apoptosis. This was accomplished by CTLs induced by a DNA vaccine encoding secretory chemokine CCL21 and the inhibitor of apoptosis protein survivin, overexpressed by both proliferating endothelial cells in the tumor vasculature and tumor cells. Oral delivery of this DNA vaccine by doubly attenuated Salmonella typhimurium (dam- and AroA-) to such secondary lymphoid organs as Peyer's patches in the small intestine, elicited marked activation of antigen-presenting dendritic cells, and an effective CD8 + T cell immune response against the survivin self-antigen. This resulted in eradication or suppression of pulmonary metastases of non-small cell lung carcinoma in both prophylactic and therapeutic settings in C57BL/6J mice. Moreover, the suppression of angiogenesis induced by the vaccine did not impair wound healing or fertility of treated mice. It is anticipated that such novel DNA vaccines will aid in the rational design of future strategies for the prevention and treatment of cancer.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalCancer research
Volume65
Issue number2
StatePublished - Jan 15 2005

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DNA Vaccines
Apoptosis
Lung
Neoplasms
Chemokine CCL21
Inhibitor of Apoptosis Proteins
Neoplasm Metastasis
Peyer's Patches
Autoantigens
Antigen-Presenting Cells
Salmonella typhimurium
Inbred C57BL Mouse
Non-Small Cell Lung Carcinoma
Wound Healing
Dendritic Cells
Small Intestine
Fertility
Vaccines
Endothelial Cells
Joints

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Xiang, R., Mizutani, N., Luo, Y., Chiodoni, C., Zhou, H., Mizutani, M., ... Reisfeld, R. A. (2005). A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication. Cancer research, 65(2), 553-561.

A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication. / Xiang, Rong; Mizutani, Noriko; Luo, Yunping; Chiodoni, Claudia; Zhou, He; Mizutani, Masato; Ba, Yi; Becker, Juergen C.; Reisfeld, Ralph A.

In: Cancer research, Vol. 65, No. 2, 15.01.2005, p. 553-561.

Research output: Contribution to journalArticle

Xiang, R, Mizutani, N, Luo, Y, Chiodoni, C, Zhou, H, Mizutani, M, Ba, Y, Becker, JC & Reisfeld, RA 2005, 'A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication', Cancer research, vol. 65, no. 2, pp. 553-561.
Xiang R, Mizutani N, Luo Y, Chiodoni C, Zhou H, Mizutani M et al. A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication. Cancer research. 2005 Jan 15;65(2):553-561.
Xiang, Rong ; Mizutani, Noriko ; Luo, Yunping ; Chiodoni, Claudia ; Zhou, He ; Mizutani, Masato ; Ba, Yi ; Becker, Juergen C. ; Reisfeld, Ralph A. / A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication. In: Cancer research. 2005 ; Vol. 65, No. 2. pp. 553-561.
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