PD-L1 Antibody and VEGF Antagonist Combination Therapy
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Solution Overview
Problem
Current cancer treatments fail to effectively enhance T-cell immunity, particularly in cancers where PD-L1 is overexpressed, leading to impaired antitumor immune responses due to the PD-1 axis signaling pathway's inhibition, necessitating a combination therapy to overcome this challenge.
Innovation Solution
A combination treatment comprising oxaliplatin, leucovorin, 5-FU, and a PD-1 axis binding antagonist, specifically an anti-PD-L1 antibody with a heavy chain and light chain variable region sequence, along with a VEGF antagonist, to inhibit PD-L1 binding to PD-1 and B7-1, enhancing T-cell function and immune response against cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PD-L1 axis binding antagonists are used to block PD-1 signaling, then T-cell immunity is enhanced, but tumor cells overexpressing PD-L1 can still evade immune surveillance through alternative mechanisms
Solution Approach 1:
The patent combines PD-L1 axis binding antagonists with VEGF antagonists in a combination therapy regimen. This merging of two different therapeutic mechanisms addresses the limitation of single-agent therapy by simultaneously blocking PD-1 signaling to enhance T-cell immunity while inhibiting VEGF to prevent tumor angiogenesis and immune evasion, thereby overcoming tumor resistance to monotherapy.
2Reliability
If combination therapy with multiple agents is used, then anti-tumor efficacy is improved, but treatment complexity increases
Solution Approach 1:
The patent segments the combination therapy into distinct administrative phases and dosage regimens. The treatment protocol divides the administration of PD-L1 axis binding antagonists and VEGF antagonists into specific cycles and sequences, making the complex combination therapy manageable through structured segmentation of treatment stages, dosage schedules, and monitoring intervals.
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 combination therapy significantly reduces tumor growth, achieves sustained anti-tumor effects, and delays cancer progression in melanoma, colorectal, non-small cell lung, ovarian, breast, prostate, and renal cell carcinomas, with potential for sustained responses even after treatment cessation.
Implementation Method 1
an anti-PD-L1 antibody comprising a heavy chain and a light chain variable region sequence, wherein (a) the heavy chain comprises an HVR-H1, HVR-H2 and HVR-H3... wherein said anti-PD-L1 antibody inhibits the binding of PD-L1 to both PD-1 and B7-1
Data Source
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AI summary
The present invention describes combination treatment comprising a PD-1 axis binding antagonist, chemotherapy and optionally a VEGF antagonist and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer.