CLEVER-1 Tumor Staining for Anti-CLEVER-1 Patient Selection
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Solution Overview
Problem
Current methods for identifying cancer patients that respond to checkpoint inhibitors and the PD-1/PD-L1 axis are approved for clinical use, but existing technologies fail to address the need for identifying patients that respond to anti-CLEVER-1 therapy, and other novel immunotherapies.
Innovation Solution
An immunohistochemistry staining method using a specific antibody which is suitable for machine reading and does not cause background color which may disturb machine reading of the stained samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If immunohistochemistry staining is performed to identify CLEVER-1 expressing cells, then patient identification accuracy is improved, but background color interference worsens machine reading capability
Solution Approach 1:
The patent applies color change principle by selecting a detection antibody conjugated with a fluorescent marker that emits at a specific wavelength, and choosing a counterstain with non-overlapping emission spectrum. This allows the specific staining signal to be distinguished from background nuclear counterstaining, enabling accurate machine reading while maintaining high patient identification accuracy.
Solution Approach 2:
The patent introduces a fluorescently labeled detection antibody as an intermediary between the CLEVER-1 antigen and the detection system. This intermediary allows specific binding to CLEVER-1 expressing cells while producing a detectable signal that can be differentiated from background staining through spectral separation, resolving the contradiction between staining visibility and machine reading accuracy.
2Measurement precision
If a specific staining antibody is used for machine reading, then reading accuracy is improved, but background color that disturbs machine reading increases
Solution Approach 1:
The patent resolves background color interference by selecting fluorescent markers with distinct emission spectra that do not overlap with the counterstain. The detection antibody is conjugated with a fluorophore whose emission can be selectively filtered, allowing the reading system to distinguish specific CLEVER-1 staining from background nuclear counterstaining, thereby maintaining high reading accuracy while minimizing background interference.
3Adaptability or versatility
If anti-CLEVER-1 therapy is administered to all cancer patients, then treatment coverage is improved, but unnecessary treatments increase
Solution Approach 1:
The patent applies preliminary action by performing immunohistochemistry staining on tumor tissue samples before administering anti-CLEVER-1 therapy. This preliminary detection of CLEVER-1 expression status in tumor-infiltrating macrophages allows clinicians to identify patients who are likely to respond to treatment, enabling targeted therapy administration and avoiding unnecessary treatments in patients who would not benefit.
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 accurately identifies cancer patients with at least 1% CLEVER-1 expressing intra-tumoral cells, allowing for effective anti-CLEVER-1 therapy, reducing unnecessary treatments.
Implementation Method 1
detecting the presence of CLEVER-1 expressing cells in a tumor sample obtained from a cancer patient by immunohistochemistry staining
Data Source
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.