PD-1/PD-L1 Antibody Immunotherapy With PD-L1 Biomarker Selection
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Solution Overview
Problem
Current cancer immunotherapies face challenges in identifying mechanism-based predictive biomarkers for patient selection and guiding treatment management, particularly in targeting the PD-1/PD-L1 signaling pathway, which is crucial for enhancing efficacy and minimizing adverse effects.
Innovation Solution
Administering therapeutically effective amounts of antibodies that disrupt the PD-1/PD-L1 signaling pathway, with biomarker-based patient selection using PD-L1 expression levels, specifically through anti-PD-1 and anti-PD-L1 antibodies like nivolumab and BMS-936559, to enhance immunotherapy efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-1 immunotherapy is administered to all cancer patients, then some patients may benefit from treatment, but treatment efficacy cannot be predicted and resources are wasted on unsuitable patients
Solution Approach 1:
The patent applies preliminary action by performing PD-L1 expression assessment on tumor tissue samples before administering anti-PD-1 immunotherapy. This pre-treatment biomarker evaluation identifies suitable patients in advance, allowing clinicians to predict treatment efficacy and avoid administering ineffective therapy to unsuitable patients, thereby resolving the contradiction between treatment efficacy prediction and lack of biomarker information
Solution Approach 2:
The patent implements feedback by using PD-L1 expression levels as a biomarker to guide treatment decisions. The assessment of PD-L1 surface expression provides feedback information about patient suitability, enabling clinicians to adjust treatment strategies based on predicted response, thus improving reliability of treatment efficacy prediction while utilizing available biomarker information
2Measurement precision
If PD-L1 expression assessment is performed on all patients, then suitable candidates can be identified, but diagnostic complexity and time increase
Solution Approach 1:
The patent applies local quality by focusing the PD-L1 expression assessment specifically on tumor tissue samples rather than performing comprehensive whole-body or multi-parameter evaluations. This targeted approach to measuring PD-L1 expression on tumor cells provides sufficient patient selection accuracy while minimizing diagnostic procedure complexity by concentrating resources on the most relevant tissue and marker
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 method induces durable clinical responses in advanced and metastatic cancers by potentiating the endogenous immune response, with PD-L1 expression thresholds guiding treatment decisions, thereby improving treatment outcomes.
Implementation Method 1
administering a therapeutically effective amount of an antibody that disrupts the PD-1/PD-L1 signaling pathway
Data Source
AI summary
The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.