Fas Axis Antagonist and Treg Depletion Therapy for Relapse Prevention
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Solution Overview
Problem
Current anti-CD25 antibody-based therapies for cancer treatment show limited response rates and are prone to tumor relapse, necessitating improved treatment regimens to enhance patient survival and prevent tumor recurrence.
Innovation Solution
Combining Treg cell depletion therapy with a Fas axis antagonist, such as an anti-CD25 antibody and an anti-FasL antibody, to maintain an immunogenic tumor microenvironment and enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-CD25 antibody-based therapy is used for cancer treatment, then Treg cell depletion is achieved, but tumor relapse occurs and patient survival is limited
Solution Approach 1:
The patent combines anti-CD25 antibody-based Treg cell depletion therapy with FasL axis modulation therapy. This combination merges two distinct therapeutic mechanisms: one targeting Treg cells directly and another modulating FasL expression on tumor cells and immune cells, thereby achieving synergistic effects that prevent tumor relapse and improve patient survival beyond what either therapy achieves alone
Solution Approach 2:
The FasL axis serves as an intermediary mechanism in this combination therapy. By modulating FasL expression and activity, the therapy creates an intermediate effect that enhances the overall therapeutic outcome. The FasL modulation acts as a mediator between Treg cell depletion and the final anti-tumor response, preventing relapse through enhanced immune activation and tumor cell apoptosis
2Productivity
If Treg cell depletion therapy is administered, then initial tumor growth is inhibited, but therapeutic efficacy is limited and tumor relapse subsequently occurs
Solution Approach 1:
The combination therapy ensures continuous useful action by maintaining both Treg cell depletion and FasL axis modulation throughout the treatment course. This continuous dual-action approach prevents the temporary nature of single-therapy responses, ensuring sustained tumor growth inhibition and preventing relapse through ongoing immune system activation and tumor cell elimination
Solution Approach 2:
The therapy employs a composite approach by integrating multiple therapeutic agents with different mechanisms of action. The anti-CD25 antibody and FasL modulating agents work together as a composite treatment system, where each component contributes different functional aspects: Treg depletion provides immediate growth inhibition while FasL modulation provides durable relapse prevention
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
The combination therapy effectively prevents tumor relapse and improves patient survival by maintaining a high Teff/Treg cell ratio, enhancing the therapeutic effectiveness of Treg cell depletion.
Implementation Method 1
blocking the Fas/FasL interaction with an inhibitor of the FasL/Fas signalling system, for example with an anti-FasL antibody or an anti-Fas antibody, may inhibit Fas-mediated cell death of activated Teffs
Implementation Method 2
Depletion of Regulatory T cells (Tregs) with antibodies against CD25 has shown to be effective in various cancer mouse models
Data Source
AI summary
The present disclosure is directed to the combination of a Fas axis antagonist, such as an anti-FasL antibody, and a Treg cell depletion therapy, for example an anti-CD25 antibody, optionally with a cancer vaccine, for use in the treatment of cancer.