Heterodimeric PSMA/CD3 Antibodies for High-PSMA Cell Selectivity
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Solution Overview
Problem
Current antibody-based therapies for prostate cancer, particularly those targeting Prostate Specific Membrane Antigen (PSMA), face challenges such as inherent toxicity and lack of selective targeting of high-PSMA expressing cells, limiting their efficacy.
Innovation Solution
Development of bispecific antibodies that bind to both CD3 and PSMA, featuring optimized binding domains with high affinity for PSMA-expressing cells, minimizing reactivity on low-expressing cells, and utilizing engineered variable regions to enhance selective targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody-based therapies target PSMA with high affinity, then therapeutic efficacy is improved, but toxicity increases and selective targeting of high-PSMA expressing cells is reduced
Solution Approach 1:
The patent applies local quality by creating heterodimeric antibodies with asymmetric binding domains where one arm binds PSMA with high affinity and the other binds CD3, allowing selective targeting of high-PSMA expressing cells while distributing the binding load to reduce toxicity
Solution Approach 2:
The patent changes binding parameters by engineering variable regions with optimized affinity constants, creating antibodies that bind PSMA with controlled affinity levels to achieve therapeutic efficacy while minimizing off-target effects and toxicity
2Measurement precision
If bisspecific antibodies are engineered to bind both CD3 and PSMA, then selective targeting of high-PSMA expressing cells is improved, but device complexity increases
Solution Approach 1:
The patent segments the antibody structure into distinct binding domains, with separate variable regions engineered to bind PSMA and CD3 independently, allowing precise control over binding specificity and reducing cross-reactivity
Solution Approach 2:
The patent creates composite antibody structures by combining heterodimeric heavy chains with different variable regions, forming a unified molecule that integrates multiple binding specificities while maintaining structural integrity
Data Source
AI summary
Provided herein are novel antigen binding domains and antibodies (e.g., heterodimeric antibodies) that bind Prostate Specific Membrane Antigen (PSMA). In exemplary embodiments, the anti-PSMA antibodies also bind CD3. Such antibodies that bind PSMA and CD3 are useful, for example in the treatment of PSMA-related cancer.