Cross-Reactive CD3-Binding Antibodies With Reduced Effector Function
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Solution Overview
Problem
Current anti-CD3 antibodies are not specific enough for human CD3, leading to side effects and limitations in therapeutic applications for human diseases, particularly due to their lack of cross-reactivity with non-human mammals like cynomolgus monkeys, which complicates preclinical testing and safety evaluation.
Innovation Solution
Development of CD3-binding molecules comprising antigen-binding fragments with specific VL and VH domains that can immunospecifically bind to both human and non-human CD3, including cynomolgus monkey CD3, and are designed to lack or reduce effector function, allowing for reduced side effects and improved therapeutic efficacy in humans.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-CD3 antibodies are used, then T cell activation and therapeutic effect are achieved, but side effects increase and specificity decreases
Solution Approach 1:
The patent applies local quality by modifying specific regions of the antibody molecule (constant regions and framework regions) while preserving the variable regions that bind CD3. This allows the antibody to maintain T cell activation capability through the variable regions while reducing non-specific binding and side effects through modifications in the constant and framework regions, thereby achieving localized optimization of therapeutic properties
2Reliability
If current anti-CD3 antibodies are used, then therapeutic effect is achieved, but cross-reactivity with non-human mammals is lost
Solution Approach 1:
The patent achieves universality by designing antibodies with modified constant and framework regions that maintain functionality across different species. The variable regions are engineered to recognize conserved epitopes on CD3 molecules from both human and non-human mammals, while the modified constant regions reduce species-specific immune responses, enabling the same antibody to function effectively in both preclinical animal models and clinical human applications
3Ease of operation
If current anti-CD3 antibodies are used, then T cell activation is achieved, but preclinical testing accuracy decreases
Solution Approach 1:
The patent uses modified constant and framework regions as intermediaries that bridge the gap between preclinical animal models and clinical human applications. These modified regions reduce non-specific binding and species-specific immune responses, allowing antibodies to behave more consistently across different species, thereby improving the predictive accuracy of preclinical testing while maintaining the desired T cell activation effect
Data Source
AI summary
The present invention relates to CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey). The invention also pertains to uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions.