A Novel Recombinant Fusion Protein Encoding a 20-Amino Acid Residue of the Third Extracellular (E3) Domain of CCR2 Neutralizes the Biological Activity of CCL2

作者：Izhak Liat; Wildbaum Gizi; Zohar Yaniv; Anunu Rachel; Klapper Leah; Elkeles Adi; Seagal Jane; Yefenof Eitan; Ayalon Soffer Michal; Karin Nathan^*

来源：The Journal of Immunology, 2009, 183(1): 732-739.

DOI：10.4049/jimmunol.0802746

CCL2 is a key CC chemokine that has been implicated in a variety of inflammatory autoimmune diseases and in tumor progression and it is therefore an important target for therapeutic intervention in these diseases. Soluble receptor-based therapy is a known approach for neutralizing the in vivo functions of soluble mediators. Owing to the complexity of seven-transmembrane G protein-coupled receptors, efforts to generate neutralizing soluble chemokine receptors have so far failed. We developed a strategy that is based on the generation of short recombinant proteins encoding different segments of a G protein-coupled receptor, and tested the ability of each of them to bind and neutralize its target chemokine. We show that a fusion protein comprised of as few as 20 aa of the third extracellular (E3) domain of the CCL2 receptor, stabilized by the IgG H chain Fc domain (E3-IgG or BL-2030), selectively binds CCL2 and CCL16 and effectively neutralizes their biological activities. More importantly, E3-IgG (BL-2030) could effectively suppress the in vivo biological activity of CCL2, attenuating ongoing experimental autoimmune encephalomyelitis, as well as the development of human prostate tumor in SCID mice. The Journal of Immunology, 2009, 183: 732-739.

• 出版日期2009-7-1