A novel brick for bispecific antibody construction

Area of Science:

• Biopharmaceutical industry
• Antibody engineering
• Protein structure-function relationship

Background:

• Bispecific antibodies (bsAbs) offer unique therapeutic potential beyond conventional monoclonal antibodies.
• The structural format of bsAbs critically influences their binding affinity, antigen interaction, and overall efficacy.
• Optimizing bsAb structure is key to unlocking novel therapeutic mechanisms.

Purpose of the Study:

• To introduce and validate a novel basic module bispecific antibody (bsAb) format, termed VFV (Variable domain-Fab-Variable domain).
• To demonstrate the versatility of the VFV format in constructing various bsAbs with potential therapeutic applications.
• To explore the VFV module as a foundational element for future bsAb drug development.

Main Methods:

• Development of the novel VFV (Variable domain-Fab-Variable domain) basic module for bispecific antibodies.
• Construction and characterization of VFV-based bsAbs, including VFV-Ig, VFV-Fab, and VFV-Hinge formats.
• Engineering a T cell engager bsAb using the VFV format to address on-target, off-tumor activity.

Main Results:

• Successful creation and validation of the VFV bsAb format.
• Demonstrated adequate purity and activity across various VFV-based bsAb constructs.
• Engineered a VFV T cell engager with potential to mitigate on-target, off-tumor effects, validating the VFV module's utility.

Conclusions:

• The VFV module represents a novel and versatile building block for constructing diverse bispecific antibodies.
• This new bsAb format expands the available toolkit for antibody engineering and drug development.
• Further research is warranted to fully establish the VFV format as a viable platform for therapeutic bsAb development.