Suppression of murine melanoma growth by a vaccine of attenuated Salmonella carrying heat shock protein 70 and Herpes simplex virus-thymidine kinase genes

Abstract

Abstract. Attenuated Salmonella can invade tumor cells and acts as a eukaryotic expression vector for gene propagation. We constructed a bi-gene, eukaryotic co-expression DNA vaccine of Mycobacterium tuberculosis heat shock protein 70 (mtHSP70) and Herpes simplex virus-thymidine kinase (HSV-tk) and used attenuated Salmonella as a vector to treat murine melanoma. In vitro, recombinant Salmonella can carry plasmid stably and can invade into the cytoplasm of B16 tumor cells expressing the protein of the mtHSP70/HSV-tk gene by Western blot assay. In vivo, after the recombinant Salmonella was injected into tumors, the HSV-tk precursor drug ganciclovir (GCV) was administered to start the HSV-tk killing of tumor cells. We found that the mtHSP70/HSV-tk recombinant bacteria can raise CD8 + T lymphocytes in peripheral blood by flow cytometry and in tumor tissues by immunofluorescence detection, increase IFN-γ contents in tumor tissue by ELISA and significantly suppress tumor growth.

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

“…A similar study using Bifidobacterium infantis as the HSVtk-expression vector showed similar anti-tumor activity in a rat model of bladder cancer [ 113 ]. Moreover, a co-expression, bi-gene GDPT system was investigated by Zeng et al , 2012 [ 111 ]. Melanoma-bearing mice were administered with S. Typhimurium co-expressing Mycobacterium tuberculosis heat shock protein 70 (mtHS70) and HSVtk, and upon administering GCV, increased IFN-γ levels within tumor tissue and marked tumor growth retardation was observed.…”

Targeted Cancer Therapy Using EngineeredSalmonella typhimurium

“… 91 Immunostimulating molecules such as glycoprotein (gp100) or heat shock protein ( M. tuberculosis heat shock protein 70) elicit host-derived protective immunity to suppress tumor development. 92 93 …”