Tissue Factor Antibody-Drug Conjugate for Selective Tumor Targeting
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Solution Overview
Problem
Existing anti-TF antibodies and ADCs exhibit interference with coagulation and cause side effects, limiting their efficacy in cancer therapy due to non-specific targeting of TF on both tumor and normal tissues.
Innovation Solution
Development of a novel TF antibody and ADC with high binding affinity and specificity for tumor cells, minimizing effects on TF-mediated coagulation, characterized by specific CDR sequences in the heavy and light chain variable regions, and a cytotoxic or cytostatic drug conjugate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing anti-TF antibodies and ADCs are used to target TF on tumor cells, then tumor targeting capability is improved, but coagulation interference and side effects occur due to non-specific binding on normal tissues
Solution Approach 1:
The patent applies local quality by engineering the antibody to have different binding characteristics at different locations: high affinity for TF on tumor cells (via specific CDR sequences) and minimal interference with TF-mediated coagulation on normal tissues. This is achieved through rational design of the CDR regions to distinguish between tumor-associated TF and physiological TF.
Solution Approach 2:
The patent changes the binding parameters of the antibody by modifying the CDR sequences to achieve optimal balance between tumor targeting affinity and coagulation interference minimization. Specific amino acid substitutions in the CDR regions alter the binding characteristics to preferentially recognize tumor cell TF while sparing normal tissue TF function.
2Adaptability or versatility
If anti-TF antibodies are designed to bind TF on both tumor and normal tissues, then broad target coverage is achieved, but side effects increase due to coagulation system interference
Solution Approach 1:
The patent segments the TF antibody binding function into distinct components: the CDR regions are specifically engineered to recognize tumor-associated TF conformations or epitopes that differ from normal tissue TF, while the Fc region maintains standard effector functions. This segmentation allows selective targeting without broad coagulation interference.
3Reliability
If existing ADCs are administered to achieve tumor growth inhibition, then therapeutic efficacy is improved, but tolerance and safety are reduced due to coagulation-related side effects
Solution Approach 1:
The patent converts the potential harm of TF binding into a benefit by exploiting the difference between tumor TF and normal tissue TF. The antibody is designed to bind tumor TF with high affinity to deliver therapeutic effect, while the same binding characteristics inadvertently minimize interference with normal coagulation TF, thus converting what could be a source of side effects into a selectivity advantage.
Data Source
AI summary
The present invention relates to an antibody and an antibody-drug conjugate, and particularly to an antibody and an antibody-drug conjugate (ADC) targeting the tissue factor, and a composition comprising the antibody or ADC, and a therapeutic application thereof.