PD-1 Binding Proteins Block Immune Suppression
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Solution Overview
Problem
Current cancer immunotherapies face challenges in effectively targeting the programmed cell death-1 (PD-1) receptor, which is involved in cancer progression and immune suppression, as existing therapies have limitations in modulating immune responses and overcoming PD-1-mediated inhibition of T-cell function.
Innovation Solution
Development of recombinant antigen-binding proteins, such as antibodies and chimeric antigen receptors, specifically designed to bind and block the PD-1 receptor, inhibiting its interaction with PD-L1, thereby enhancing T-cell activation and immune response against cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing cancer immunotherapies target PD-1 receptor, then immune response modulation is achieved, but therapeutic efficacy is limited due to PD-1-mediated inhibition of T-cell function
Solution Approach 1:
The patent converts the harmful PD-1 immune suppression mechanism into a beneficial therapeutic effect by developing antibodies that block PD-1 receptor binding to PD-L1 ligand. This prevents the inhibitory signal transmission, thereby converting the harmful immune suppression into enhanced T-cell activation and anti-tumor immune response, achieving therapeutic efficacy in cancer treatment
2Reliability
If recombinant antigen-binding proteins are designed to block PD-1 receptor, then T-cell activation is enhanced, but complexity of protein design and production increases
Solution Approach 1:
The patent uses recombinant DNA technology to create copies of antibody genes encoding specific variable regions (such as those shown in SEQ ID NOS: 28-30, 49-51) that recognize PD-1 receptor. These gene copies are inserted into expression vectors and produced in host cells, allowing scalable production of the therapeutic proteins while maintaining consistent binding specificity and activity
Solution Approach 2:
The patent develops chimeric antigen receptors (CARs) that combine multiple functional domains into a single protein construct. The CAR includes an extracellular antigen-binding domain, a transmembrane domain, and intracellular signaling domains, enabling T-cells to simultaneously recognize tumor antigens and receive activation signals, thereby enhancing T-cell activation efficacy while providing a comprehensive solution in a single molecular entity
Data Source
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AI summary
The present application provides constructs comprising an anti-PD-1 antigen-binding protein or a fragment thereof, as well as nucleic acids or CAR T cells expressing such antigen-binding protein or fragment. Also provided are methods of regulating T cells or treating patients using such constructs or cells.