Inhibition of Cancer Cell Adhesion, Migration and Proliferation by a Bispecific Antibody that Targets two Distinct...

Area of Science:

• Integrin biology and antibody engineering
• Molecular mechanisms of cancer and fibrosis

Background:

• Alpha-v (αv) integrins are key regulators of transforming growth factor beta (TGFβ) activation.
• These integrins are implicated in pro-tumorigenic phenotypes and fibrotic processes.
• Developing selective αv integrin inhibitors presents a significant therapeutic challenge.

Purpose of the Study:

• To generate selective antibodies targeting αv integrins using phage display.
• To engineer a bispecific antibody with enhanced inhibitory function.
• To evaluate the therapeutic potential of the bispecific antibody in cancer models.

Main Methods:

• Phage display selections were performed on cell lines expressing αv integrin heterodimers.
• Antibodies targeting distinct αv integrin epitopes were identified and characterized.
• A bispecific antibody was engineered by combining paratope sequences from selected antibodies.

Main Results:

• Synthetic antibodies targeting two distinct αv integrin epitopes were isolated.
• The engineered bispecific antibody potently inhibited cell adhesion mediated by αvβ1, αvβ3, and αvβ5 integrins.
• The bispecific antibody demonstrated significant inhibition of lung carcinoma cell proliferation and migration.

Conclusions:

• Phage display with live cells is an effective strategy for generating high-quality anti-integrin antibodies.
• The developed bispecific antibody exhibits strong inhibition of αv integrin function.
• This bispecific antibody represents a promising therapeutic candidate for cancer and fibrosis.