"Two-in-One" approach for bioassay selection for dual specificity antibodies

Area of Science:

• Biotechnology and Pharmaceutical Sciences
• Immunology and Therapeutics

Background:

• Dual specific antibodies and bispecific antibodies are advanced therapeutics for complex human diseases, targeting two distinct antigens.
• Developing bioassay strategies for these antibodies presents challenges in reflecting mechanism of action (MoA) and measuring dual activities.

Purpose of the Study:

• To present a novel single bioassay approach for dual specific antibodies targeting two receptors in signaling pathways.
• To demonstrate an assay capable of measuring antibody effects on both target bindings simultaneously.

Main Methods:

• Development of a single bioassay for a dual specific monoclonal antibody (mAb1) targeting two receptors.
• Implementation of an assay development and bridging study strategy.
• Evaluation of the assay's ability to detect changes in binding to either target.

Main Results:

• The single bioassay successfully measures antibody effects on both target bindings, a feat not achievable with two separate assays.
• The assay demonstrates improved sensitivity, enabling the substitution of two binding assays for lot release and stability testing.
• The approach ensures consistency between lots by measuring any changes in either target binding.

Conclusions:

• A single, MoA-reflective bioassay can effectively assess dual specific antibodies targeting two receptors.
• This approach simplifies testing, enhances sensitivity, and ensures therapeutic consistency.
• The demonstrated strategy is potentially applicable to other dual specific, bispecific antibodies, and antibodies used in combination therapy.