Secretable Immunomodulatory Proteins for Synapse Targeting
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Solution Overview
Problem
Current immunotherapies for modulating the immune response, such as those targeting the immunological synapse, are limited by the inability of soluble receptors and antibodies to simultaneously bind multiple targets with high affinity and spatial specificity, failing to effectively activate or inhibit immune cells in a manner consistent with the complex interactions within the synapse.
Innovation Solution
Development of immunomodulatory proteins with affinity-modified immunoglobulin superfamily domains that specifically bind to cell surface cognate partners, engineered to be secreted or expressed on cells, allowing for enhanced or attenuated immunological activity by modulating interactions at the immunological synapse, including binding to both stimulatory and inhibitory receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If soluble receptors are used to antagonize protein interactions, then immune response modulation is achieved, but the ability to agonize interactions is lost
Solution Approach 1:
The patent uses antibodies instead of soluble receptors to achieve immune response modulation. Antibodies can be engineered to exhibit either agonistic or antagonistic effects by targeting specific epitopes, thereby inverting the limitation of soluble receptors and providing versatility in both activating and blocking immune interactions.
Solution Approach 2:
The patent modifies the parameters of antibody molecules through genetic engineering to alter their binding affinity, specificity, and functional effects. By changing amino acid sequences and structural parameters, the antibodies can be tuned to produce desired agonistic or antagonistic effects on immune cell interactions.
2Adaptability or versatility
If antibodies are used to provide both agonistic and antagonistic effects, then versatility is improved, but the ability to simultaneously bind multiple targets with high affinity and spatial specificity is lost
Solution Approach 1:
The patent segments the immunomodulatory function into separate antibody molecules, each designed to target specific receptors with high spatial specificity. Rather than attempting to make a single antibody bind multiple targets simultaneously, multiple specialized antibodies are used to achieve coordinated immunomodulation while maintaining precise spatial binding at each target site.
Solution Approach 2:
The patent employs a universal platform of engineered antibodies that can be configured to perform different functions (agonistic or antagonistic) by targeting different receptors. This multi-functional antibody platform allows simultaneous modulation of multiple immune pathways while each individual antibody maintains high spatial specificity for its designated target.
3Reliability
If cell surface proteins interact with multiple protein targets simultaneously, then complex immunological synapse functions are achieved, but soluble agents cannot replicate this coordinated interaction
Solution Approach 1:
The patent uses engineered antibodies as intermediary molecules that mediate interactions between immune cells and their target receptors. These antibody intermediaries can simultaneously engage multiple receptors on cell surfaces, replicating the coordinated multi-protein interactions of the immunological synapse while providing the flexibility and specificity of soluble agents.
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
These proteins effectively modulate immune cell activity by increasing or decreasing immunological responses, providing a novel therapeutic approach that can simultaneously activate or inhibit immune cells, addressing the limitations of existing therapies by maintaining spatial and temporal specificity within the immunological synapse.
Implementation Method 1
the at least one affinity-modified IgSF domain specifically binds at least one cell surface cognate binding partner of the wild-type IgSF domain
Data Source
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AI summary
Provided are immunomodulatory proteins, nucleic acids encoding such immunomodulatory proteins, cells engineered to express the immunomodulatory proteins and infections agents containing nucleic acid encoding the immunomodulatory proteins. In some embodiments, the immunomodulatory proteins are secretable. In some embodiments, the immunomodulatory proteins are transmembrane proteins that are surface expressed. The immunomodulatory proteins, engineered cells and infectious agents provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.