GITR-Binding Monoclonal Antibody with Enhanced ADCC
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Solution Overview
Problem
There is a lack of therapeutic antibodies that specifically bind to GITR and effectively activate the receptor to enhance immune responses against tumors, as current antibodies in clinical trials are limited and no approved therapies exist.
Innovation Solution
Development of a monoclonal antibody or antigen-binding fragment that specifically binds to GITR, comprising specific CDR sequences in the heavy and light chain variable domains, with enhanced ADCC properties to activate the receptor and inhibit regulatory T cells, thereby boosting the immune response against tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antibodies in clinical trials are used, then some immune activation effect is achieved, but they lack specific binding to GITR and effective receptor activation to enhance immune responses against tumors
Solution Approach 1:
The patent develops monoclonal antibodies with specifically engineered CDR sequences (CDR1, CDR2, CDR3 of heavy chain and CDR1, CDR2, CDR3 of light chain) that bind to GITR with high specificity and affinity. The antibodies are designed to activate GITR receptor signaling, thereby enhancing immune responses against tumors while maintaining specific binding to the target receptor
2Object-affected harmful factors
If GITR is expressed on both immune cells and tumor cells, then the antibody can target tumor cells directly, but it may also affect normal immune cell function
Solution Approach 1:
The patent exploits the differential expression patterns of GITR on various cell types to achieve selective therapeutic effects. By designing antibodies that specifically bind to and activate GITR, the treatment enhances immune responses in a controlled manner while the Fc region modifications ensure selective depletion of regulatory T cells rather than all immune cells expressing GITR
3Productivity
If regulatory T cells suppress effector T cells, then immune response is dampened, but enhancing effector T cell activity may lead to excessive immune activation
Solution Approach 1:
The patent uses GITR as an intermediary target to indirectly regulate the balance between regulatory T cells and effector T cells. The monoclonal antibodies bind to GITR on Tregs and induce selective depletion of these suppressive cells through ADCC, thereby releasing the suppression on effector T cells and enhancing anti-tumor immunity without causing excessive immune activation
4Manufacturing precision
If monoclonal antibodies are engineered with specific CDR sequences for high affinity binding, then binding specificity is improved, but antibody production and manufacturing complexity increases
Solution Approach 1:
The patent divides the antibody structure into distinct functional segments: variable regions with specifically engineered CDR sequences for high-affinity GITR binding, and Fc regions with modified amino acid sequences for enhanced ADCC activity and selective Treg depletion. This segmentation allows independent optimization of binding specificity and effector function while facilitating standardized manufacturing processes
Data Source
AI summary
The present invention relates to biotechnology, in particular to antibodies or antigen-binding fragments thereof, and to use thereof. More particularly, the present invention relates to monoclonal antibodies that specifically bind to GITR. The invention also relates to a nucleic acid encoding said antibody or antigen-binding fragment thereof, an expression vector, a method for preparing said antibody, and use of said antibody in treatment of diseases or disorders associated with GITR.