NK Cell Dysfunction Detection via CD56 and Calcium Mobilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
B- and T-cell acute lymphoblastic leukemia (B/T-ALL) is aggressive and often recurs after therapy due to therapeutic resistance, primarily caused by suppression of anti-leukemia host immunity, particularly the dysfunction of natural killer (NK) cells.
Innovation Solution
A method is provided to identify dysfunctional NK cells in leukemia patients by detecting elevated expression levels of CD56 and CD94, an elevated ratio of CD11b−CD27− to CD11b+CD27− NK cells, the presence of CD69, cytokines, or calcium mobilization in the NK cell population.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapy is used for B/T-ALL, then initial response may be achieved, but therapeutic resistance develops and leukemia recurs
Solution Approach 1:
The patent applies feedback by detecting NK cell dysfunction markers (CD56, CD94, CD69 expression levels and calcium mobilization) to assess patient response to therapy and predict relapse risk. This feedback mechanism enables dynamic adjustment of treatment strategies based on real-time immune surveillance status, addressing the contradiction between initial therapeutic response and long-term remission duration.
Solution Approach 2:
The patent implements preliminary action by identifying dysfunctional NK cells before leukemia recurrence occurs. Through proactive detection of NK cell markers and calcium mobilization patterns, the system enables preventive interventions to restore immune surveillance functionality, thereby extending remission duration and preventing therapeutic resistance.
2Object-generated harmful factors
If NK cell function is suppressed to treat leukemia, then cancer cells are eliminated, but anti-leukemia host immunity is compromised
Solution Approach 1:
The patent uses NK cell dysfunction markers (CD56, CD94, CD69) and calcium mobilization as intermediary indicators to assess the balance between leukemia elimination and host immunity preservation. These markers serve as mediators that enable monitoring of immune surveillance status without directly interfering with the therapeutic process, allowing clinicians to maintain effective cancer treatment while preserving anti-leukemia immunity.
Solution Approach 2:
The system employs feedback mechanisms through continuous monitoring of NK cell marker expression and calcium mobilization to assess host immunity status. This feedback enables dynamic adjustment of therapy to maintain the optimal balance between eliminating leukemia and preserving anti-cancer immune responses, preventing excessive immunosuppression.
3Measurement precision
If NK cell dysfunction is detected using multiple markers, then identification accuracy is improved, but detection complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the NK cell dysfunction detection into distinct marker categories (CD56, CD94, CD69 expression levels and calcium mobilization). This segmentation allows systematic evaluation of multiple parameters independently, improving detection accuracy while maintaining organizational clarity and reducing analytical complexity through structured assessment protocols.
Solution Approach 2:
The patent implements universality by developing a multi-marker detection system that can identify NK cell dysfunction across different leukemia subtypes and treatment stages. The unified approach using CD56, CD94, CD69 and calcium mobilization markers provides broad applicability for monitoring NK cell function in various clinical scenarios, improving detection accuracy without requiring subtype-specific complex assays.
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
This method effectively identifies dysfunctional NK cells, which are associated with leukemia recurrence, allowing for targeted therapeutic interventions, such as administering allogeneic NK cells or engineered NK cells to enhance immune surveillance and treatment efficacy.
Implementation Method 1
detecting... (f) calcium (Ca2+) mobilization
Data Source
AI summary
Provided herein are, inter alia, methods for identifying dysfunctional natural killer (NK) cells in a subject with leukemia. Provided are methods for treating leukemia, including administering to the subject an effective amount of allogeneic NK cells.