Anti-angiogenesis effect on glioma of attenuatedSalmonella typhimurium vaccine strain with flk-1 gene

Abstract

To investigate the anti-vasculature effects and the anti-glioma effects of attenuatedSalmonella typhimurium vaccine strain expressing VEGFR2 (flk-1) gene, plasmid pcDNA3, 1-flk1 was constructed and electro-transfected into live attenuatedSalmonella typhimurium strain SL7207. Mouse models of intracranial Gl261 glioblastoma were treated with an orally administered attenuatedSalmonella typhimurium expressing flk-1 gene. The survival period was recorded and vessel density was observed by immunofluorescence. CTLs activity was measured by MTT assay. Our results showed that attenuatedSalmonella typhimurium vaccine strain expressing flk-1 gene could significantly inhibit glioblastoma growth, reduce vessel density, prolong the survival period and improve the survival rate in these mice. The flk-1 specific CTLs activity was increased obviously after the vaccination. Our study showed that attenuatedSalmonella typhimurium vaccine strain expressing flk-1 gene could break peripheral immune tolerance a in glioma gainst this self-antigen and kill endothelial cells by the orally administered vaccine and can be used for both prophylactic and therapeutic purposes.

Keywords

attenuatedSalmonella typhimurium / flk-1 / glioma

References

[1] AbdollahiA, LipsonK E, HanX, et al. . SU5416 and SU6668 attenuate the angiogenic effects of radiation-induced tumor cell growth factor production and amplify the direct anti-endothelial action of radiation in vitro. Cancer Res, 2003, 63(13): 3755-3755

[2] HelenS G, KateF G, KatherineA B, et al. . Oral immunisation with livearoA attenuated protects mice a gainst plague. Vaccine, 2003, 213051-3051

[3] FolkmanJ. Can mosaic tumor vessels facilitate molecular diagnosis of cancer?. Proc Natl Acad Sci (USA), 2001, 98398-398

[4] LiuJ Y, WeiY Q, YangL, et al. . Immunotherapy of tumors with vaccine based on quail homologous vascular endothellal growth factor receptor-2. Blood, 2003, 102(5): 1815-1815

[5] SirardJ C, NiedergangF, KrachenbuhlJ P, et al. . Live attenuated Salmonella: a paradigm of mucosal vaccines. Immunol Rev, 1999, 1715-5

[6] NichthammerA G, PrimusF J, XiangR, et al. . An cral DNA vaccine against humancarcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice. Vaccine, 2001, 20(3–4): 421-421