A novel bispecific diabody targeting both vascular endothelial growth factor receptor 2 and epidermal growth factor...

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are key targets in cancer therapy.
• Their signaling pathways are often co-activated in various tumors, driving tumor growth and angiogenesis.
• Targeting both pathways simultaneously may offer a more effective therapeutic strategy.

Purpose of the Study:

• To design and characterize a bispecific diabody (bDAb) targeting both EGFR and VEGFR2.
• To evaluate the in vitro and in vivo efficacy of this novel bispecific diabody (EK-02).
• To assess its potential as a cotargeted therapy for EGFR and VEGFR2 overexpressing tumors.

Main Methods:

• Production and characterization of a bispecific diabody (EK-02) targeting EGFR and VEGFR2.
• In vitro assays using HUVEC, A431, and HT29 cell lines to assess binding, proliferation, migration, and apoptosis.
• In vivo studies using a chicken chorioallantoic membrane (CAM) tumor model to evaluate anti-angiogenesis and anti-tumor effects.

Main Results:

• EK-02 demonstrated binding to cells expressing high levels of VEGFR2 and EGFR.
• The bDAb inhibited cell proliferation and migration while inducing apoptosis, retaining parental antibody functions.
• EK-02 showed enhanced efficacy in inhibiting HT29 cell growth, migration, and inducing apoptosis compared to parental antibodies.
• In vivo, EK-02 effectively inhibited neovascularization and tumor formation in the CAM model.

Conclusions:

• The bispecific diabody EK-02 possesses significant anti-angiogenesis and anti-tumor capacity.
• EK-02 demonstrates efficacy both in vitro and in vivo.
• This novel bDAb holds promise for cotargeted therapy in tumors overexpressing EGFR and VEGFR2.