Anti-DR5 Antibody Selectivity and Stability Optimization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic agents targeting death receptor 5 (DR5) for cancer treatment face challenges such as low selectivity and stability issues, with recombinant TRAIL inducing apoptosis in both cancer and normal cells, and previous anti-DR5 antibodies showing limited efficacy and adverse effects.
Innovation Solution
Development of a TRAIL-uncompetitive anti-DR5 antibody that specifically binds to DR5, retaining antigen binding activity irrespective of TRAIL concentrations, and is designed to induce apoptosis in cancer cells without affecting normal cells, utilizing specific polypeptide sequences for targeted therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant TRAIL is used as a therapeutic agent, then it can bind to death receptors to induce apoptosis, but it binds non-specifically to multiple receptors (DR4, DR5, DcR1, DcR2) causing low selectivity and adverse effects on normal cells
Solution Approach 1:
The patent extracts the apoptotic function from TRAIL by developing anti-DR5 antibodies that specifically target only DR5 receptor, separating the desired cancer-killing function from the harmful non-specific binding to DcR1, DcR2, and DR4 receptors that causes adverse effects in normal cells
Solution Approach 2:
The patent introduces anti-DR5 antibodies as intermediary agents that mediate the apoptotic signal specifically at DR5 receptors on cancer cells, avoiding direct TRAIL binding to multiple receptors and thereby preventing off-target effects on normal cells
2Reliability
If recombinant TRAIL is used to treat cancer, then it can induce apoptosis in cancer cells, but it has poor stability
Solution Approach 1:
The patent creates antibody copies that mimic TRAIL's ability to bind DR5 and induce apoptosis, but with improved stability characteristics. The anti-DR5 antibodies serve as stable alternatives to the unstable recombinant TRAIL protein while maintaining the desired cytotoxic function
3Reliability
If previous anti-DR5 antibodies (HGS-ETR2, Apomab, Conatumumab, tigatuzumab) are used for cancer treatment, then they target DR5 specifically, but they show limited efficacy and have adverse effects
Solution Approach 1:
The patent changes the binding parameters of anti-DR5 antibodies by developing novel variable regions with optimized affinity and specificity. This results in antibodies that maintain high DR5 specificity while achieving superior cancer cell killing efficacy compared to previous generations of anti-DR5 antibodies
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 anti-DR5 antibody effectively induces cancer cell death with enhanced selectivity and stability, offering superior efficacy compared to previous antibody drugs and diagnostic agents, while minimizing adverse effects on normal cells.
Implementation Method 1
TRAIL or antibodies bind to DR5 to form a Death-Inducing Signaling Complex (DISC)
Implementation Method 2
which through the adaptor protein (FADD) activates the apoptosis-initiating proteases caspase-8 and caspase-10
Data Source
AI summary
The present invention relates to an antibody that specifically binds to death receptor 5 (DR5) and has a function of killing cancer cells. Specifically, provided are an anti-DR5 antibody or antigen-binding fragment thereof, and a use of the antibody or antigen-binding fragment for preventing or treating cancer. The present invention is characterized in that the anti-DR5 antibody or antigen-binding fragment thereof is improved in terms of affinity to DR5, stability, and an effect of killing cancer cells.