IL-5Rα×CD3ε Bispecific Antibody for T Cell-Mediated Eosinophil Depletion
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Solution Overview
Problem
Current bispecific antibodies targeting IL-5Rα for eosinophil reduction have limitations in efficacy, toxicity, and availability, and there is a need for pharmaceuticals that can induce more potent eosinophil reduction without increasing IL-5 half-life or causing resistance.
Innovation Solution
Development of IL-5Rα×CD3ε T cell-engaging bispecific antibodies using heterodimeric Fc technology, combining the 5R65.7 antibody targeting IL-5Rα with high affinity and the SP34 antibody targeting CD3ε, to induce T cell-mediated cytotoxicity against eosinophils.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If current bispecific antibodies targeting IL-5Rα are used for eosinophil reduction, then eosinophil depletion is achieved, but efficacy is limited and IL-5 half-life increases
Solution Approach 1:
The patent introduces T cells as intermediary effector cells that mediate eosinophil depletion through cytotoxicity. The bispecific antibody acts as a mediator that bridges IL-5Rα-expressing eosinophils and CD3-expressing T cells, enabling T cell-mediated killing without directly interacting with IL-5, thus avoiding the side effect of prolonged IL-5 half-life while achieving effective eosinophil depletion
Solution Approach 2:
The patent extracts the eosinophil depletion function from the IL-5/IL-5Rα binding interaction itself and transfers it to a T cell-mediated cytotoxicity mechanism. By separating the target recognition (anti-IL-5Rα) from the effector mechanism (T cell engagement via anti-CD3), the patent achieves eosinophil reduction without the adverse effect of increased IL-5 half-life that occurs with direct IL-5 neutralization
2Quantity of substance
If current bisspecific antibodies targeting IL-5Rα are used, then eosinophil depletion is achieved, but resistance develops and toxicity occurs
Solution Approach 1:
The patent uses T cells as intermediary effector cells that provide a more reliable and sustainable mechanism for eosinophil depletion. By engaging the robust T cell immune system rather than relying solely on direct antibody-antigen neutralization, the patent reduces the likelihood of resistance development and minimizes toxicity associated with direct IL-5 pathway blockade
Solution Approach 2:
The patent harnesses the body's own T cell immune system to perform eosinophil depletion autonomously. Once the bisspecific antibody bridges T cells and eosinophils, the T cells self-organize and execute cytotoxicity without requiring continuous external intervention, providing a reliable and sustainable depletion mechanism that is less prone to resistance
3Quantity of substance
If T cell-mediated cytotoxicity is induced through bispecific antibody, then eosinophil reduction is enhanced, but antibody complexity increases
Solution Approach 1:
The patent designs a bisspecific antibody that performs multiple functions: it recognizes IL-5Rα on eosinophils, recruits CD3-expressing T cells, and enables T cell-mediated cytotoxicity. This multi-functional molecule achieves enhanced eosinophil reduction while consolidating multiple therapeutic mechanisms into a single antibody structure, managing complexity through functional integration
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The bispecific antibodies effectively induce T cell-mediated cytotoxicity, leading to enhanced eosinophil reduction and potential therapeutic benefits for allergic and inflammatory diseases.
Implementation Method 1
The present invention relates to a T cell engaging bispecific antibody. More specifically, the present invention relates to a humanized antibody that simultaneously binds to a human T cell marker (CD3) and human IL-5 receptor alpha subunit (IL-5Rα)
Data Source
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AI summary
The present invention relates to a T cell engaging bispecific antibody. More particularly, the present invention relates to: a bispecific antibody that simultaneously binds to human interleukin-5 (IL-5) receptor alpha subunit (IL-5Rα), which is a receptor of human IL-5, and CD3ε, which is a human T cell marker; a nucleic acid encoding same; a vector comprising the nucleic acid; a cell transformed with the vector; a method for producing the bispecific antibody or; a composition comprising same for the prevention or treatment of allergic diseases, inflammatory diseases, and/or diseases caused by an increase in eosinophils; and a composition comprising same for the diagnosis of allergic diseases, inflammatory diseases, and/or diseases caused by an increase in eosinophils.