LAG3 Binding Peptides for Immune Checkpoint Modulation
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Solution Overview
Problem
There is a need for effective modulators of immune checkpoint pathways, particularly targeting Lymphocyte Activation Gene 3 (LAG3), to enhance anti-tumor immunity and treat synucleinopathies.
Innovation Solution
Development of peptides that bind to LAG3, blocking its interaction with MHC-II, FGL1, and α-synuclein, which can be administered alone or in conjunction with other therapies such as CAR-T cells or oncolytic viruses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If LAG3 binds to MHC-II, then immune checkpoint signaling is activated, but anti-tumor immunity is suppressed
Solution Approach 1:
The patent uses peptides as intermediary molecules that bind to LAG3 with high affinity, acting as mediators to displace the LAG3-MHC-II interaction. These peptide intermediaries competitively bind to LAG3's ligand-binding site, preventing the harmful signaling while maintaining reliable immune checkpoint modulation.
Solution Approach 2:
The invention extracts the critical ligand-binding region of LAG3 and creates peptide mimics that replicate this binding interface. By taking out the essential binding motifs and synthesizing them as discrete peptide molecules, the patent enables selective disruption of LAG3-MHC-II interaction without affecting other LAG3 functions.
2Reliability
If LAG3 binds to FGL1, then immune regulation occurs, but anti-tumor immunity is reduced
Solution Approach 1:
The patent employs peptides as intermediary agents that specifically target and bind to LAG3's FGL1 interaction site. These peptide mediators compete with FGL1 for binding to LAG3, thereby regulating immune function through controlled peptide-LAG3 interactions while blocking the harmful FGL1-mediated immunosuppression.
3Reliability
If LAG3 binds to α-synuclein aggregates, then neuronal signaling is affected, but synucleinopathy symptoms worsen
Solution Approach 1:
The patent uses peptides as intermediary molecules that bind to LAG3's α-synuclein binding site, acting as mediators to prevent pathological α-synuclein aggregation and neuronal signaling disruption. These peptide intermediaries sequester LAG3 in a controlled manner, blocking the harmful interaction with α-synuclein aggregates while preserving essential neuronal functions.
4Reliability
If monoclonal antibodies are used to block LAG3, then immune checkpoint inhibition is achieved, but treatment complexity and cost increase
Solution Approach 1:
The patent replaces complex, expensive monoclonal antibodies with simpler, shorter-lived peptide molecules that perform the same LAG3-blocking function. These peptides are cheaper to produce, easier to administer, and can be rapidly synthesized and modified, reducing treatment complexity and cost while maintaining effective immune checkpoint inhibition.
Solution Approach 2:
The invention changes the molecular parameters from large protein-based monoclonal antibodies to smaller peptide molecules. This parameter change includes reducing molecular weight, simplifying structure, and optimizing pharmacokinetic properties, thereby achieving comparable therapeutic efficacy with reduced complexity and improved deliverability.
Data Source
AI summary
This disclosure provides nucleic acids encoding peptides which bind to LAG3 and can be used to block the interaction of LAG 3 with other molecules such as MHC-II, FGL1, and α-synuclein. These peptides can be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer, or inhibiting the progression of a synucleinopathy, inhibiting the progression of sepsis, inhibiting the progression of an infectious disease, and enhancing a response to a vaccine.