Anti-PD-l1 combinations for treating tumors
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Solution Overview
Problem
Current therapeutic antibodies face challenges in achieving long-term efficient inhibition and killing of tumor cells due to issues such as antibody immunogenicity, tolerance of long-term use of tumor targets, and limitations in signal transduction pathway blockade, while antibody-drug conjugates face difficulties in delivering toxins effectively to tumor cells.
Innovation Solution
A combination therapy involving a PD-L/PD-1 Axis antagonist, such as anti-PD-1 or anti-PD-L1 antibodies, and an immunotherapeutic like Resiquimod, which activates plasmacytoid dendritic cells, myeloid dendritic cells, or NK cells, is administered to enhance immune response against tumors without being linked to each other.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic antibodies are used to block tumor targets, then tumor cell inhibition is achieved, but long-term efficiency decreases due to antibody immunogenicity and target tolerance
Solution Approach 1:
The patent combines PD-L/PD-1 axis antagonists with immunotherapeutics (TLRLs) that activate dendritic cells and NK cells. This merging of two different therapeutic mechanisms - direct tumor target blockade and immune system activation - creates a synergistic effect that overcomes the limitations of single-therapy approaches, maintaining long-term tumor inhibition despite target tolerance development
Solution Approach 2:
The patent introduces dendritic cells and NK cells as intermediary elements that bridge the antibody therapy and tumor cell destruction. These immune cells are activated by TLRLs and serve as mediators to enhance and sustain the anti-tumor response, preventing the decline in effectiveness that occurs with long-term direct antibody blockade alone
2Strength
If antibody-drug conjugates are used to deliver toxins, then direct tumor cell killing is enhanced, but delivery effectiveness decreases due to technical requirements and tumor microenvironment limitations
Solution Approach 1:
The patent uses dendritic cells and NK cells as intermediary carriers to deliver toxic effects to tumor cells. Instead of directly conjugating toxins to antibodies that face delivery challenges, the immunotherapeutic activates these immune cells which then naturally seek out and destroy tumor cells, bypassing the delivery limitations of antibody-drug conjugates
Solution Approach 2:
The patent replaces the mechanical/chemical delivery system of antibody-drug conjugates with a biological system involving activated immune cells. The TLRL-activated dendritic cells and NK cells use biological recognition and cytotoxic mechanisms rather than direct chemical toxin delivery, overcoming the technical constraints of conjugate stability and tumor microenvironment penetration
3Productivity
If simple signal transduction pathway blockade is used, then initial tumor response is achieved, but long-term killing efficiency decreases
Solution Approach 1:
The patent transitions from a static signal blockade mechanism to a dynamic immune activation system. The TLRL immunotherapeutic dynamically activates dendritic cells and NK cells that can adapt and sustain their anti-tumor activity over time, unlike the static antibody blockade that tumors can easily overcome through tolerance mechanisms
Solution Approach 2:
The patent enables the patient's own immune system to serve the anti-tumor function. By activating dendritic cells and NK cells through TLRLs, the body's natural immune mechanisms are harnessed to continuously identify and eliminate tumor cells, creating a self-sustaining therapeutic effect that doesn't rely on continuous external antibody administration
Data Source
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AI summary
The present invention relates to therapeutic combinations and methods for treating cancers using combination therapy.