Tumor T Cell Phenotype Selection for Persistent ACT Response
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Solution Overview
Problem
The impact of T cell phenotype on the clinical success of adoptive cell therapy (ACT) for cancer treatment has not been fully elucidated, necessitating improved methods to prepare cell populations for ACT.
Innovation Solution
A method to obtain a cell population enriched for T cells with a phenotype comprising markers CD3+, CD8+, CD39-, and CD69-, involving selection and isolation of T cells from tumor samples based on these markers, followed by administering the enriched population to patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cells are selected based on phenotype markers CD39- and CD69- to improve ACT effectiveness, then treatment efficacy and T cell persistence are improved, but the complexity of cell selection and characterization increases
Solution Approach 1:
The patent applies parameter changes by defining specific phenotypic markers (CD39 and CD69 expression levels) to identify and select T cells with desired functional properties. By establishing quantitative criteria for marker expression, the patent transforms the complex biological selection process into a measurable and controllable parameter-based system, resolving the contradiction between treatment efficacy and selection complexity.
Solution Approach 2:
The patent replaces manual or empirical T cell selection methods with a standardized phenotypic characterization system based on flow cytometry or similar technologies. This substitution allows for objective, reproducible identification of CD39- CD69- T cells, improving reliability while making the selection process more systematic and less complex.
2Duration of action of moving object
If T cell phenotype is not characterized, then the process is simpler and faster, but the clinical success and persistence of ACT cannot be ensured
Solution Approach 1:
The patent applies preliminary action by performing phenotypic characterization of T cells before adoptive cell therapy administration. By assessing CD39 and CD69 marker expression in advance, the patent identifies T cells with optimal persistence potential, ensuring long-term effectiveness while streamlining the preparation process through predefined selection criteria.
Solution Approach 2:
The patent enables self-service by allowing the T cell population to effectively select itself based on inherent phenotypic characteristics. The CD39- CD69- marker profile serves as a natural identifier for T cells with desired persistence properties, eliminating the need for complex external selection mechanisms and maintaining preparation efficiency.
3Reliability
If all T cell populations are administered without selection, then the procedure is simpler and more cost-effective, but the response to ACT is inconsistent and less effective
Solution Approach 1:
The patent applies parameter changes by establishing specific phenotypic parameters (CD39 and CD69 expression levels) as selection criteria for T cells. This transforms the cell preparation process from an unselected bulk approach to a parameter-defined selective approach, ensuring consistent clinical response while maintaining procedural simplicity through standardized marker assessment.
Data Source
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AI summary
Disclosed are methods of obtaining a cell population enriched for T cells with a phenotype, the method comprising: (a) obtaining a bulk population of T cells from a tumor sample of a patient; (b) specifically selecting T cells with a phenotype comprising markers CD3+, CD39-, and CD69- from the bulk population; and (c) separating the cells selected in (b) from cells which lack the phenotype to obtain a cell population enriched for T cells with the phenotype. Related methods of treating or preventing cancer, methods of selecting a therapy for a cancer patient, and methods for predicting the clinical response to immunotherapy in a cancer patient are also disclosed. Isolated or purified cell population obtained according to the methods and related pharmaceutical compositions are also disclosed.