CLEVER-1 Tumor Staining for Anti-CLEVER-1 Patient Selection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods fail to accurately identify cancer patients who will respond to anti-CLEVER-1 therapy, leading to unnecessary treatments and inefficiencies.
Innovation Solution
A method using immunohistochemistry staining with a specific antibody to detect CLEVER-1 expressing cells in tumor biopsies, calculating a threshold of at least 1% of CLEVER-1 positive cells to determine patient responsiveness to anti-CLEVER-1 treatment, preferably with anti-CLEVER-1 antibody bexmarilimab.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If immunohistochemistry staining is used to detect CLEVER-1 expressing cells, then patient identification accuracy is improved, but background color interference may occur that disturbs machine reading
Solution Approach 1:
The patent extracts and removes the harmful background color signal from the immunohistochemistry staining process. Specifically, it uses a two-tone DAB staining system where one tone indicates CLEVER-1 positive cells and another tone indicates negative cells or background, allowing the machine reading system to distinguish and exclude background interference from the measurement, thereby maintaining high measurement precision without background color disturbance
Solution Approach 2:
The patent employs color changes as the core mechanism for detection and differentiation. By using DAB chromogen that produces distinct color tones (brown for positive, blue for negative/background) in the immunohistochemistry staining, the system enables machine reading algorithms to accurately differentiate between specific CLEVER-1 expressing cells and background tissue, resolving the contradiction between detection accuracy and background interference
2Reliability
If anti-CLEVER-1 therapy is administered to all cancer patients, then more patients may benefit, but unnecessary treatments increase reducing efficiency
Solution Approach 1:
The patent applies preliminary action by performing immunohistochemistry staining and machine reading analysis on tumor tissue samples before administering anti-CLEVER-1 therapy. This pre-treatment identification process determines CLEVER-1 expression levels and predicts treatment response in advance, allowing clinicians to selectively treat only those patients likely to benefit, thereby avoiding unnecessary treatments and optimizing resource allocation while maintaining high treatment effectiveness
Solution Approach 2:
The patent implements a feedback mechanism where the machine reading system quantifies CLEVER-1 expression levels from stained tissue images and provides this information back to guide treatment decisions. The system establishes a threshold for CLEVER-1 positive cells that predicts treatment response, creating a feedback loop that connects biomarker measurement to therapeutic decision-making, ensuring that treatment is administered only to patients with sufficient CLEVER-1 expression
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
Accurately identifies patients likely to benefit from anti-CLEVER-1 therapy, reducing unnecessary treatments and improving treatment response by targeting those with sufficient CLEVER-1 expression levels.
Implementation Method 1
detecting the presence of CLEVER-1 expressing cells in a tumor sample obtained from a cancer patient by immuno-histochemistry staining
Data Source
Figure 1~2
Figure 3
Figure 4
AI summary
A method for pre-treatment identification of cancer patients that respond to anti-CLEVER-1 therapy comprising an administration of an agent capable of binding to CLEVER-1 in a patient. In the method, the presence of CLEVER-1 expressing cells is detected in a tumor sample obtained from a cancer patient, by immunohistochemistry staining by a mouse monoclonal IgG2a kappa STAB-1 antibody (clone 4G9), and a percentage of intra-tumoral CLEVER-1 expressing cells from the total amount of viable intra-tumoral cells present in the stained sample is calculated. A tumor sample which shows substantial percentage of CLEVER-1 expressing intra-tumoral cells is an indication that the cancer patient is responsive to the anti-CLEVER-1 therapy.