Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk

In metastatic cancer, activation of the HER receptor and crosstalk with other RTKs, especially HER-MET crosstalk, are important reasons for tumor resistance to anti-HER receptor therapy. In this chapter, FL518 (four-in-one antibody) and DVD-Ig CRTB6 (tetravalent specific antibody) were developed, which can recognize EGFR, HER2, HER3, and VEGF while simultaneously inhibiting HER-MET crosstalk. Compared with bispecific antibodies, four-in-one antibodies can inhibit the growth of drug-resistant tumor cells with MET overactivation more effectively. In conclusion, this study provides a new idea to use a single antibody to inhibit HER activation and limit the occurrence of drug resistance.