Oral DNA vaccine expressing xenogeneic EGFR inhibits growth of Lewis lung cancer in mice
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Abstract:
Objective:To investigate the inhibitory effect of attenuated salmonella typhimurium vaccine, which expressing xenogeneic chicken EGFR and IgG γFc, on the growth of Lewis lung cancer (expressed high level of EGFR)-implanted tumors in mice. Methods: pVAX1/ cEGFR-γFc plasmid was transformed into attenuated salmonella typhimurium strain SL7207, and the resultant SL7207/pVAX1-cEGFR-γFc bacteria were used to infect murine peripheral macrophage in vitro. Then expression of cEGFR-γFc fusion protein was detected by immunofluorescent assay. Mice were immunized with SL7207/pVAX1-cEGFR-γFc for 3 times, and then inoculated with Lewis cells. Expression of cEGFR-γFc fusion protein in mice tissue was detected by Western blotting analysis, and serum anti-EGFR level was determined by ELISA method. The weight of implanted Lewis tumor was measured after 14 d to investigate the anti-tumor effect of SL7207/pVAX1-cEGFR-γFc vaccine, and the survival time of tumor-bearing mice was also examined. Results: The attenuated salmonella typhimurium DNA vaccine SL7207/pVAX1- cEGFR-γFc was successfully constructed. The cEGFR-γFc fusion protein could be expressed in mouse cells after SL7207/pVAX1-cEGFR-γFc infection in vitro and in vivo. The mice immunized with SL7207/pVAX1-cEGFR-γFc could produce high level of anti-EGFR antibody. The tumor growth was obviously inhibited and the survival time of tumor-bearing mice was also increased in the SL7207/pVAX1-cEGFR-γFc vaccine group. Conclusion: The DNA vaccine expressing xenogeneic EGFR can effectively inhibit the growth of EGFR-positive tumors, which is a new EGFR-targeting therapy strategy.
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Project supported by the Foundation of Shanghai Science Committee (No. 03DZ19263), and the Foundation of Health Bureau of Putuo District in Shanghai (No.PTW08-Z01)