ST2 Antibody Targeting Effector Treg Cells in Tumors
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Solution Overview
Problem
Current cancer immunotherapies face challenges in overcoming immunosuppression by effector Treg cells, which impede anti-tumor immune responses and limit the effectiveness of treatments like immune checkpoint inhibitors.
Innovation Solution
The methods involve reducing or inhibiting ST2 and IL-33 signaling in Treg cells using pharmacological inhibitors or genetic ablation, such as CRISPR-Cas systems, to decrease Treg cell activity and increase CD8+ T cell infiltration into tumors, employing antibodies or antibody fragments that block ST2 and IL-33 signaling and induce ADCC against Treg cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Treg cells are depleted to enhance anti-tumor immunity, then anti-tumor immune response is improved, but systemic autoimmunity occurs
Solution Approach 1:
The patent applies local quality by making Treg cells heterogeneous through differential expression of ST2 and other markers, allowing selective targeting of tumor-infiltrating Tregs with anti-ST2 antibodies while sparing peripheral Tregs that maintain immune tolerance, thus achieving local immunosuppression reversal without systemic autoimmunity
Solution Approach 2:
The patent uses anti-ST2 antibodies as intermediaries to selectively deplete tumor-infiltrating Tregs. The ST2 marker serves as a specific identifier that allows the antibody to target and remove suppressive Tregs in the tumor microenvironment without affecting peripheral Tregs, thereby mediating selective immunosuppression reversal
2Reliability
If immune checkpoint inhibitors are used to treat cancer, then response rate is improved in some patients, but effectiveness is limited by other immunosuppressive mechanisms
Solution Approach 1:
The patent merges immune checkpoint inhibition with Treg depletion strategies by combining anti-PD-1/PD-L1 antibodies with anti-ST2 antibodies. This combination therapy addresses multiple immunosuppressive mechanisms simultaneously - checkpoint blockade removes inhibitory signals on effector T cells while Treg depletion eliminates suppressive cells, creating synergistic anti-tumor immunity
Solution Approach 2:
The patent develops a universal approach that can be applied across different cancer types and in combination with various immunotherapies. The anti-ST2 antibody mechanism works independently of specific tumor antigens or checkpoint pathways, making it broadly applicable to enhance the effectiveness of immunotherapies across diverse cancer indications
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 effectively reduces immunosuppression, enhances CD8+ T cell infiltration into tumors, and inhibits tumor growth by decreasing the levels and activities of effector Treg cells, thereby improving cancer treatment outcomes.
Implementation Method 1
the agents can be antibodies or antibody fragments thereof that specifically bind to ST2 and/or IL-33 proteins. The binding of antibody to ST2 and/or IL-33 can lead to blocking of ST2/IL-33 signaling pathway
Implementation Method 2
The binding of antibody to ST2 can result in an antibody-dependent cell-mediated cytotoxicity (ADCC) that will destroy the Treg cells bound by the anti-ST2 antibody or antibody fragments thereof
Implementation Method 3
For genetic ablation, it can be performed using CRISPR-Cas system, RNAi system, zinc finger nucleases, TALEN system, meganucleases, or any combination thereof
Data Source
AI summary
The present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Treg cells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Treg cells in a tumor microenvironment are inhibited, and the infiltration of effector CD8+ cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Treg cells in a population of heterogeneous cells.