The bispecific antibody is a novel antibody， which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here， we designed and synthesized a bispecific antibody (BsAb) that can bind cellular-mesenchymal to epithelial transition factor (c-MET， overexpressed in several human solid tumor)， and programmed death-1 (PD-1， involved in cancer cell immune evasion) with high affinity and specificity. We found that BsAb can induce the degradation of c-MET protein in cancer cells， including MKN45， a gastric cancer cell line， and A549， a lung cancer cell line. BsAb inhibited hepatocyte growth factor (HGF)-mediated proliferation... More
The bispecific antibody is a novel antibody， which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here， we designed and synthesized a bispecific antibody (BsAb) that can bind cellular-mesenchymal to epithelial transition factor (c-MET， overexpressed in several human solid tumor)， and programmed death-1 (PD-1， involved in cancer cell immune evasion) with high affinity and specificity. We found that BsAb can induce the degradation of c-MET protein in cancer cells， including MKN45， a gastric cancer cell line， and A549， a lung cancer cell line. BsAb inhibited hepatocyte growth factor (HGF)-mediated proliferation， migration， and antiapoptosis， and downregulated HGF-stimulated phosphorylation of c-MET， protein kinase B (AKT)， and extracellular signal-regulated kinase (ERK1/2). BsAb can also rescue T cell activation. Furthermore， xenograft analysis revealed that BsAb markedly inhibits the growth of subcutaneously implanted tumors and chronic inflammation. On the basis of these results， we have identified a potential bispecific drug， which can effectively target c-MET and PD-1 for the treatment of human solid cancers.
