Enhanced anti-tumor effect of an IFN-gamma-EGF fusion protein.
The novel fusion proteins harboring human or mouse interferon combined with epidermal growth factor receptor binding domain were constructed using methods of genetic and protein engineering. The fusion proteins were assayed to retain complete antiviral activities. The EGF receptor binding moiety of the fusion proteins exhibited competitive binding against 125I-EGF for EGF receptors on A431 cells. The fusion proteins were shown to be more potent in inhibiting the growth of cultured target carcinoma cells than interferon-gamma alone. Experimental data derived from mouse B16 malignant melanoma models indicates that the weight of tumor in mice treated with IFN fusion proteins was significantly smaller than that of mice treated with interferon-gamma alone. The work here is unprecedented in the world and provides a reliable evidence to support the upcoming clinical employment of a class of interferons that specifically target tumor cell.
Chen
W Q
WQ
National Laboratory of Molecular Virology and Genetic Engineering, Chinese Academy of Preventive Medicine, Beijing, China.
Ding
Y P
YP
Zhang
L L
LL
Hou
Y D
YD
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D066246:ErbB Receptors