GITR Antigen Binding Proteins for Immune Activation
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Solution Overview
Problem
Current immunotherapies lack effective agents that can specifically activate the Glucocorticoid-induced TNFR-related gene (GITR) to enhance immune responses, particularly in treating cancers and infections where increased immune activation is desirable.
Innovation Solution
Development of antigen binding proteins, such as antibodies or antibody fragments, that specifically bind to GITR, mimicking the natural ligand GITRL, to induce or enhance GITR signaling, thereby activating immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies are used, then general immune modulation is achieved, but specific activation of GITR to enhance immune responses is not achieved
Solution Approach 1:
The patent introduces antigen binding proteins (antibodies) as intermediary molecules that specifically bind to GITR on T cells, mimicking the natural ligand GITRL. These antibodies serve as mediators to transmit the activating signal specifically to GITR, enabling reliable immune response enhancement with high specificity that conventional immunotherapies cannot achieve
Solution Approach 2:
The patent develops multiple antibody variants with different affinity parameters and binding characteristics. By optimizing binding affinity (KD values) and other parameters, the antibodies achieve both high specificity for GITR and reliable immune activation, resolving the contradiction between general modulation and specific activation
2Productivity
If GITR activation is enhanced to increase effector T cell response, then immune activation is improved, but regulatory T cell suppression may be intensified
Solution Approach 1:
The patent employs antibodies with varying affinity levels and dosing strategies that create dynamic control over GITR activation. By adjusting antibody concentration and affinity, the system can dynamically balance effector T cell activation against regulatory T cell suppression, optimizing immune response while minimizing harmful suppression
Solution Approach 2:
The patent describes antibodies with different binding affinities (ranging from high to moderate affinity) that can be selected based on the desired balance between activating effector T cells and managing regulatory T cell suppression. This parameter variation allows optimization of the activation-suppression balance for different therapeutic contexts
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 antigen binding proteins effectively activate immune responses by agonizing GITR, leading to increased effector T cell activation, reduced regulatory T cell suppression, and potential therapeutic benefits in cancer and infection treatments.
Implementation Method 1
Antigen binding proteins that bind GITR, such as human GITR, are described herein. The antigen binding proteins can be antibodies or fragments thereof... that have the ability to bind GITR
Implementation Method 2
GITR signaling functions as a co-activating signal to both CD4+ and CD8+ naïve T cells, thereby inducing or enhancing proliferation and effector function... GITR activation results in an enhanced immune response
Data Source
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Figure 2
AI summary
Antigen binding proteins that activate GITR are provided. Nucleic acids encoding the antigen binding proteins and vectors and cells containing such nucleic acids are also provided. The antigen binding proteins have value in therapeutic methods in which it is useful to stimulate GITR signaling, thereby inducing or enhancing an immune response in a subject. Accordingly, the antigen binding proteins have utility in a variety of immunotherapy treatments, including treatment of various cancers and infections.