BACKGROUND: IFN-alpha has been shown to be effective against hematologic malignancies. However, it is ineffective against most solid tumors and has not been satisfactory because of its toxicity. METHODS: The NGR (Asn-Gly-Arg) peptide is a tumor-homing peptide. In order to increase the anti-tumor activity of IFN-alpha2a and lower the dose, we coupled a cyclic NGR peptide with the C terminus of IFN-alpha2a (named IFN-alpha2a-NGR). RESULTS: The fusion protein was expressed in E. coli and purified by ion-exchange chromatography. The purity of IFN-alpha2a-NGR was >98% and the final purification yield of IFN-alpha2a-NGR was approximately 18 mg/L. The anti-tumor efficacy and the binding ability of IFN-alpha2a-NGR with tumor vasculature were investigated in vitro and in vivo. DISCUSSION: Our study has demonstrated that the anti-tumor efficacy of IFN-alpha2a-NGR is significantly increased in comparison with IFN-alpha2a, and IFN-alpha2a-NGR could selectively target tumor vessels. These data indicate that the tumor-homing peptide (NGR) can enhance the therapeutic efficacy of IFN-alpha2a against tumors.
BACKGROUND: IFN-alpha has been shown to be effective against hematologic malignancies. However, it is ineffective against most solid tumors and has not been satisfactory because of its toxicity. METHODS: The NGR (Asn-Gly-Arg) peptide is a tumor-homing peptide. In order to increase the anti-tumor activity of IFN-alpha2a and lower the dose, we coupled a cyclic NGR peptide with the C terminus of IFN-alpha2a (named IFN-alpha2a-NGR). RESULTS: The fusion protein was expressed in E. coli and purified by ion-exchange chromatography. The purity of IFN-alpha2a-NGR was >98% and the final purification yield of IFN-alpha2a-NGR was approximately 18 mg/L. The anti-tumor efficacy and the binding ability of IFN-alpha2a-NGR with tumor vasculature were investigated in vitro and in vivo. DISCUSSION: Our study has demonstrated that the anti-tumor efficacy of IFN-alpha2a-NGR is significantly increased in comparison with IFN-alpha2a, and IFN-alpha2a-NGR could selectively target tumor vessels. These data indicate that the tumor-homing peptide (NGR) can enhance the therapeutic efficacy of IFN-alpha2a against tumors.
Authors: Regina L Bis; Tara M Stauffer; Surinder M Singh; Thomas B Lavoie; Krishna M G Mallela Journal: Protein Expr Purif Date: 2014-04-30 Impact factor: 1.650