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Published on: February 2, 2018
[Anti-tumor effects of mouse factor VII-Staphylococcus enterotoxin A (mfVII) chimeric protein in mice]
Jin Li1, Ying Sun, Chen Masako
1Department of Medical Oncology, Fudan University Cancer Hospital, Shanghai 200032, China. lijin@csco.org.cn
Objective:
Mouse factor VII (mfVII), ligand of tissue factor (TF) which is frequently over-expressed during neovascularization activated by tumor growth, was fused to staphylococcus enterotoxin A (SEA) that mediates greater intensity of T-cell activation against tumor cells. The anti-tumor effects of the mfVII-SEA chimeric protein were evaluated.
Methods:
Fusion of SEA and mfVII cDNA was constructed using adenovirus vector and produced in 293 packaging cell lines. The 293 cells containing the adenovirus were administered subcutaneously to mice. Fluorescence studies at the injection site and the liver were performed 3 days later. Mouse prostatic tumor RM-1 cells and mouse sarcoma MCA 205 H12 cell lines were then used in mice to create lung metastasis and subcutaneous tumor to carry out efficacy evaluation, respectively.
Results:
Adenovirus released from the injected 293 cells only infected the subcutaneous tissue at the injection site. The in vivo experiments in mice revealed that formation of lung metastasis was strongly inhibited by the mfVII-SEA (23 +/- 8) compared to the vacant vector control group (193 +/- 38) and PBS control group (211 +/- 42) (P < 0.01). The mfVII-SEA also strongly suppressed tumor growth at the subcutaneous injection site (342.6 +/- 107.1) mm(3) compared to that of vacant vector control (2244.3 +/- 350) mm(3) and SEA (1208.3 +/- 210) mm(3) by the 23rd day.
Conclusion:
The chimeric protein mfVII-SEA significantly inhibits lung metastasis formation and local tumor growth.
