Multivalent Antibody Specificity via Competitive Binding
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Solution Overview
Problem
Current cancer treatments using multispecific antibodies often result in unwanted side effects due to binding to normal cells expressing tumor antigens, leading to toxicity and reduced tolerability, as these antigens are also present on non-tumor cells.
Innovation Solution
A composition comprising a multivalent antibody with variable domains binding to tumor antigens and an immune cell engaging antigen, combined with a second binding molecule that competes with the multivalent antibody for binding to specific tumor antigens, reducing off-target effects by enhancing binding specificity to cells expressing both antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a multivalent antibody binds to tumor antigens to activate immune cells, then the immune response against tumor is enhanced, but normal cells expressing the same antigens are also affected causing toxicity
Solution Approach 1:
The patent applies local quality by creating a multivalent antibody with distinct binding regions: one region specifically targets tumor antigens (such as EGFR) while another region targets immune cell activating molecules (such as CD3). This localized functional differentiation allows the antibody to selectively engage immune cells at the tumor site without uniformly affecting all cells expressing the target antigen, thereby reducing systemic toxicity while maintaining immune response efficacy.
Solution Approach 2:
The multivalent antibody embodies multi-functionality by simultaneously performing multiple roles: it acts as a tumor targeting agent, an immune cell recruiter, and a signal activator. By combining these functions in a single molecular entity with specific valency and orientation, the antibody achieves enhanced tumor-specific immune activation while the controlled binding properties reduce off-target effects on normal cells.
2Manufacturing precision
If the antibody binds strongly to tumor antigens to ensure target engagement, then targeting efficacy is improved, but binding to normal cells increases causing side effects
Solution Approach 1:
The patent utilizes parameter changes by carefully controlling the valency, affinity, and spatial orientation of the antibody's binding regions. By adjusting these parameters, the antibody achieves optimal binding strength to tumor antigens while the controlled valency reduces avidity effects on normal cells. This parameter optimization allows strong target engagement with sufficient selectivity to minimize binding to normal cells expressing the same antigens.
Data Source
AI summary
The invention relates to a composition comprising a multivalent antibody comprising a first variable domain that binds a first tumor antigen (TA1), a second variable domain that binds a second tumor antigen (TA2) and a third variable domain that binds an immune cell engaging antigen (IEA); and wherein the composition further comprises a second binding molecule that binds TA1 or TA2. The invention also relates to a kit of parts comprising the multivalent antibody and second binding molecule, and to means and methods for the treatment of cancer comprising administering to the subject in need thereof the multivalent antibody and second binding molecule.