Tumor-Infiltrating Treg Marker Targeting for Selective ADCC Depletion
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Solution Overview
Problem
Current cancer therapies targeting tumor-infiltrating regulatory T cells (Treg cells) face challenges such as severe autoimmunity and non-specific depletion of effector cells, necessitating a more precise and selective approach to modulate Treg cell functions in the tumor microenvironment.
Innovation Solution
Identification of specific molecular signatures on tumor-infiltrating Treg cells, such as IL1R2, PD-1 Ligand1, PD-1 Ligand2, and CCR8, allows for the development of molecules that can selectively bind and deplete these cells, inducing antibody-dependent cell-mediated cytotoxicity (ADCC) to enhance tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies deplete tumor-infiltrating regulatory T cells, then anti-tumor immune responses are enhanced, but severe autoimmunity and non-specific depletion of effector cells occur
Solution Approach 1:
The patent applies local quality by targeting specific molecular signatures (IL1R2, PD-1 Ligand1, PD-1 Ligand2, CCR8) that are selectively expressed on tumor-infiltrating Treg cells. This enables the therapeutic agent to distinguish and deplete only the pathogenic Treg population within the tumor microenvironment while preserving systemic Treg homeostasis and effector cell function, thereby resolving the contradiction between enhancing anti-tumor immunity and avoiding autoimmunity
Solution Approach 2:
The patent segments the Treg cell population by identifying distinct molecular markers that differentiate tumor-infiltrating Tregs from other T cell subsets. By targeting these specific markers, the therapy selectively eliminates the tumor-associated suppressive population while maintaining other immune cell populations intact, thus achieving selective depletion without non-specific effects
2Reliability
If broad depletion of regulatory T cells is performed, then tumor immunity is enhanced, but effector cells are non-specifically depleted
Solution Approach 1:
The patent employs local quality by utilizing the differential expression pattern of molecular signatures on tumor-infiltrating Treg cells. The therapeutic agent is designed to recognize and bind to these specific markers (particularly in combination), enabling precise targeting of the suppressive Treg population within the tumor while sparing effector T cells and other immune populations, thus achieving high depletion specificity
Solution Approach 2:
The patent uses molecular signatures as intermediaries to mediate the selective depletion process. These markers serve as recognition elements that bridge the therapeutic agent and the target Treg cells, enabling specific identification and elimination of tumor-infiltrating Tregs without affecting other cell types, thereby resolving the specificity issue
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
This approach provides a safer and more targeted method to enhance anti-tumor immune responses by selectively depleting tumor-infiltrating Treg cells, potentially improving treatment outcomes in cancers like non-small-cell lung cancer and colorectal cancer.
Implementation Method 1
molecules that can selectively bind and deplete these cells, inducing antibody-dependent cell-mediated cytotoxicity (ADCC)
Data Source
AI summary
The present invention discloses a number of markers selectively deregulated in tumor-infiltrating regulatory T cells. The invention relates to molecules able to modulate the expression and/or function of at least one such marker for use in the prevention and/or treatment of the tumor. Preferably the molecule specifically binds to the marker and induces antibody-dependent cell-mediated cytotoxicity (ADCC). The invention further relates to a molecule able to modulate the expression and/or function of at least one such marker for use in a method for in vivo depleting tumor-infiltrating regulatory T cell in a subject, or for use in a method to enhance tumor immunity in a subject. Corresponding pharmaceutical compositions are also contemplated.