Fc Region Polypeptides for Targeted Immune Activation
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Solution Overview
Problem
Current treatments for viral infections and cancer, particularly those involving herpesviruses and oncolytic therapies, face challenges in effectively activating immune effector cells and managing passive antibody-dependent cell-mediated cytotoxicity (ADCC), which can lead to adverse effects and reduced therapeutic efficacy.
Innovation Solution
Development of immunological polypeptides that bind to Fc gamma receptors on immune effector cells and non-overlapping domains on target cells, allowing for targeted activation or inhibition of ADCC without using the antigen-binding region of antibodies, thereby enhancing or inhibiting immune responses as needed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies are used to activate immune effector cells through ADCC, then immune cell activation is improved, but adverse effects increase and therapeutic efficacy is reduced
Solution Approach 1:
The patent introduces Fc fragment polypeptides as intermediary molecules that mediate between immune effector cells and target cells. These polypeptides contain an Fc region that binds to Fc gamma receptors on immune effector cells and a separate domain that binds to Fc binding proteins on target cells, thereby activating ADCC without using完整 antibodies. This intermediary approach maintains immune activation while reducing adverse effects associated with full antibody therapy.
Solution Approach 2:
The invention segments the antibody molecule into its functional components, specifically utilizing only the Fc region for immune cell activation while separating it from the antigen-binding Fab regions. By constructing polypeptides with only the necessary Fc domain and a target-binding domain, the patent achieves selective immune activation without the side effects associated with complete antibody structures.
2Measurement precision
If full antibodies are used for ADCC, then target cell recognition is improved, but device complexity increases
Solution Approach 1:
The patent extracts and utilizes only the essential Fc region of antibodies that is responsible for immune effector cell activation, while removing or separating the antigen-binding Fab regions. This extraction approach simplifies the molecular structure to only the necessary components for ADCC activation, reducing complexity while maintaining target cell recognition capabilities through alternative mechanisms.
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 polypeptides enhance the efficacy of treatments by improving immune cell activation and reducing adverse effects, allowing for more effective targeting and clearance of infected cells or tumor cells while minimizing side effects.
Implementation Method 1
an Fc region that binds to an Fc gamma receptor
Implementation Method 2
a domain that binds Fc binding proteins on target cells
Data Source
AI summary
In certain embodiments, described herein is a method of treating a subject infected with a pathogen encoding an Fc-binding protein comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody. Also described herein is a method for treating cancer in a subject undergoing oncolytic viral therapy comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody. Further described herein is a method of activating natural killer (NK) cells in a subject infected with a pathogen, comprising administering to the subject a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody.