Humanized Anti-DKK2 Antibody for CD8+ T-Cell Tumor Immunity
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Solution Overview
Problem
Current immunotherapy for cancer is not effective for subsets of patients, and there is a need for improved methods to diminish cancer cell proliferation, trigger cancer cell death, and enhance anti-cancer immunotherapy and diagnosis, particularly targeting the Wnt/β-catenin pathway.
Innovation Solution
Administration of a humanized anti-Dickkopf2 (anti-DKK2) antibody to modulate the tumor immune microenvironment, stimulate T cell-mediated immune responses, and diagnose cancer through DKK2 gene expression levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy is administered to treat cancer, then immune system stimulation is achieved, but treatment efficacy is limited to only subsets of patients
Solution Approach 1:
The patent introduces anti-DKK2 antibody as an intermediary agent that specifically targets the DKK2 protein in the Wnt/β-catenin pathway. This mediator bridges the gap between conventional immunotherapy and tumor cells by blocking DKK2-mediated inhibition of Wnt signaling, thereby enhancing immune response in tumor-specific manner and improving efficacy across broader patient populations
Solution Approach 2:
The patent modifies the immunotherapy approach by changing the molecular target parameter from general immune stimulation to specific Wnt pathway modulation via DKK2 inhibition. This parameter change enables the therapy to effectively target tumors with Wnt pathway dysregulation, expanding adaptability to different cancer types and patient subsets
2Productivity
If Wnt/β-catenin pathway is hyperactivated to promote cell growth, then cell proliferation increases, but cancer development occurs
Solution Approach 1:
The patent converts the harmful effect of DKK2 (which inhibits Wnt signaling and promotes tumor suppression) into a beneficial therapeutic target. By administering anti-DKK2 antibody to block DKK2 function, the therapy restores appropriate Wnt signaling levels, thereby converting the harmful immunosuppressive effect of DKK2 into a beneficial anti-tumor immune response while preventing uncontrolled cancer growth
3Reliability
If DKK2 expression is increased to inhibit Wnt signaling, then Wnt pathway activity decreases, but tumor formation is promoted
Solution Approach 1:
The patent inverts the conventional understanding of DKK2 function by demonstrating that blocking DKK2 (rather than allowing it to inhibit Wnt signaling) is therapeutically beneficial. The anti-DKK2 antibody blocks DKK2's ability to inhibit Wnt signaling, thereby restoring proper Wnt pathway activity and preventing tumor formation through enhanced immune surveillance and anti-tumor immunity
Data Source
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AI summary
The present invention relates to the discovery that inhibition of Dickkopf2 (DKK2) increases CD8+ cytotoxic T lymphocyte (CTL) activity, attenuates tumor, and hence suppresses tumor formation. Thus, in various embodiments described herein, the methods of the invention relate to methods of treating cancer by administering to a patient an effective amount of a humanized anti-DKK2 antibody, methods for providing anti-tumor immunity in a subject, methods of stimulating a T cell mediated immune response to a cell population or a tissue and suppressing tumor in a subject. Additionally, the current invention includes methods of diagnosing a cancer or a predisposition of developing a cancer or a metastasis and methods for determining the use of immunotherapy treatment or cancer vaccine for treating cancer. Furthermore, the invention encompasses a pharmaceutical composition for treating cancer as well as a kit for carrying out the aforementioned methods.