B-Cell Antibody Receptor for Neutralizing Antibody Suppression
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Solution Overview
Problem
Existing treatments for diseases caused by the production of neutralizing antibodies against therapeutic enzymes or coagulation factors in the body are ineffective due to immune system recognition of these agents as foreign substances, leading to reduced therapeutic efficacy.
Innovation Solution
Development of a B-cell antibody receptor (BAR) that combines an antibody binding domain, transmembrane domain, intracellular domain of a costimulatory factor, and activated receptor, specifically targeting and eliminating B cells producing neutralizing antibodies, using immune cells like αβT cells, CD8T cells, CD4T cells, γδT cells, or NK cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If replacement therapy is administered to replenish insufficient blood coagulation factors or enzymes, then the therapeutic effect is improved, but the patient's immune system recognizes the replenished factors as foreign substances and produces neutralizing antibodies, attenuating the therapeutic effect
Solution Approach 1:
The invention converts the harmful neutralizing antibodies into beneficial tools by engineering immune cells (CAR-T cells) that express chimeric antigen receptors specifically targeting these antibodies. The same antibodies that were attacking the therapeutic enzymes are now used as recognition markers to guide immune cells to eliminate the B-cells producing them, thereby converting a harmful immune response into a therapeutic mechanism.
Solution Approach 2:
The chimeric antigen receptor (CAR) acts as an intermediary between the therapeutic enzymes and the immune system. Instead of directly protecting the enzymes or suppressing the immune system broadly, the CAR serves as a mediator that specifically recognizes neutralizing antibodies through their Fc region and directs immune cell activity against the producing B-cells, enabling precise control of the immune response.
2Adaptability or versatility
If neutralizing antibodies are produced against replenished coagulation factors or enzymes, then the body's immune response is activated, but the enzyme cannot sufficiently exert its function, reducing therapeutic efficacy
Solution Approach 1:
Instead of trying to suppress the immune response or prevent antibody formation, the invention inverts the approach by harnessing the immune system's antibody-producing capability against the antibodies themselves. The CAR-T cells are designed to recognize and eliminate B-cells that produce neutralizing antibodies, turning the immune response against itself to protect the therapeutic enzymes.
Solution Approach 2:
The system establishes a feedback loop where the presence of neutralizing antibodies triggers an immune response that eliminates the producing B-cells. The CAR-T cells continuously monitor for neutralizing antibodies and respond by targeting and destroying the B-cells that produce them, creating a self-regulating system that maintains therapeutic enzyme functionality.
Data Source
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AI summary
Provided are a B-cell antibody receptor (BAR), a BAR-T cell and others which are effective for the treatment of diseases associated with antibodies produced in the bodies of patients. The B-cell antibody receptor (BAR) according to the present invention comprises (a) an antibody binding domain, (b) a transmembrane domain, (c) an intracellular domain of a costimulating factor and (d) an intracellular domain of an activated receptor which are linked together.