High-yield expression, purification and characterization of tumor-targeted IFN-alpha 2a

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-Lx2a and lower the dose, we coupled a cyclic NGR peptide with the C terminus of IFN-alpha 2a (named IFN-L alpha 2a- NGR). Results The fusion protein was expressed in E. coli and purified by ion-exchange chromatography The purity of IFN-alpha 2a-NGR was > 98% and the final purification yield of IFN-alpha 2a-NGR was approximately 18 mg/L. The anti-tumor efflicacy and the binding ability of IFN-alpha 2a-NGR with tumor vasculature were investigated in vitro and in vivo. Discussion Our study has demonstrated that the anti-tumor efficacy of IFN-alpha 2a NGR is significantly increased in comparison with IFN-alpha 2a, and IFN-alpha 2a-NGR could selectively target tumor vessels. These data indicate that the tumor-homing peptide (NGR) can enhance the therapeutic efficacy of IFN-alpha 2a against tumors.