Anti-TF Antibody-Drug Conjugate for Tumor-Selective TF Targeting
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Solution Overview
Problem
The high expression of tissue factor (TF) in various solid tumors promotes tumor growth and metastasis, and is associated with poor prognoses, necessitating a targeted therapeutic approach.
Innovation Solution
Development of an anti-TF antibody and anti-TF antibody-drug conjugate, particularly with exatecan analog, to specifically target and inhibit TF-expressing cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TF-targeted therapy is used to inhibit tumor growth, then anti-tumor efficacy is improved, but risk of thrombosis and hemorrhage increases
Solution Approach 1:
The patent applies local quality by differentiating the therapeutic action at different locations: the antibody selectively binds to TF on tumor cell surfaces (local tumor targeting) while the Fc region mediates effector functions at the tumor site. This localized action inhibits tumor growth without systemically activating coagulation pathways, thus reducing thrombosis and hemorrhage risks associated with non-specific TF inhibition.
Solution Approach 2:
The patent uses an intermediary approach by employing the Fc region as a mediator that facilitates tumor cell lysis through complement activation and antibody-dependent cellular cytotoxicity (ADCC). This intermediary mechanism allows indirect killing of tumor cells while maintaining control over the therapeutic effect, avoiding direct interference with coagulation factors and reducing bleeding risks.
2Reliability
If TF signaling pathways are blocked to prevent tumor growth, then tumor progression is inhibited, but normal physiological coagulation function may be disrupted
Solution Approach 1:
The patent achieves local quality by directing the antibody's binding specifically to TF expressed on tumor cell surfaces rather than circulating TF or TF on normal tissues. This selective localization ensures that TF signaling is blocked only in the tumor microenvironment, preserving normal coagulation function while still achieving effective tumor growth inhibition.
Solution Approach 2:
The patent applies the extraction principle by isolating and targeting only the pathogenic TF signaling in tumors through the antibody, while leaving the physiological TF-coagulation system intact. The antibody specifically extracts and neutralizes TF's pro-tumor signaling functions without interfering with its role in hemostasis, thus avoiding disruption of normal coagulation function.
Data Source
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AI summary
The present invention relates to an anti-TF antibody and an anti-TF antibody-drug conjugate and a medical use thereof. Specifically, the present invention relates to an anti-TF antibody, and an anti-TF antibody-drug conjugate represented by general formula (Pc-L-Y-D), wherein the Pc is the anti-TF antibody, and L, Y, and n are as defined in the description.