Predicting ACT Survival in EBV-Positive Nasopharyngeal Carcinoma
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Solution Overview
Problem
Current treatments for metastatic nasopharyngeal carcinoma, particularly those involving checkpoint inhibitor blockade and CAR-T therapy, lack reliable biomarkers for predicting patient response and survival, and are limited in efficacy due to an immunosuppressive tumor microenvironment.
Innovation Solution
A method for predicting long-term survival in patients undergoing adoptive cell transfer (ACT) by analyzing blood-derived samples for prognostic markers such as MDSC, Treg, and effector T lymphocyte populations, and administering targeted therapies to modulate these populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitor blockade or CAR-T therapy is used to treat metastatic NPC, then immune response is enhanced, but there is no reliable biomarker to predict patient response and survival
Solution Approach 1:
The patent performs preliminary analysis of immune cell populations (Tregs, MDSCs, effector T cells) in patient blood samples before initiating ACT therapy. This preliminary characterization of the immunosuppressive microenvironment enables prediction of treatment response and survival outcomes, resolving the lack of predictive biomarker information
Solution Approach 2:
The patent establishes feedback loops by monitoring changes in immune cell populations at multiple time points during treatment. This dynamic monitoring provides continuous information about treatment efficacy and patient response, enabling real-time prediction adjustments and informing clinical decision-making
2Duration of action of stationary object
If adoptive cell transfer is used to treat metastatic NPC, then long-term survival may be achieved, but it is difficult to identify which patients will be long-term survivors
Solution Approach 1:
The patent performs preliminary baseline characterization of immune cell populations before ACT therapy to identify patients likely to achieve long-term survival. By measuring Treg, MDSC, and effector T cell levels at baseline and during treatment, the patent predicts which patients will become long-term survivors, making the identification process straightforward rather than difficult
Solution Approach 2:
The patent replaces the mechanical/observational approach of waiting to see which patients survive with a biochemical/measurement-based predictive system. By measuring specific immune cell populations and their ratios, the patent substitutes direct long-term observation with earlier molecular biomarker assessment
3Object-affected harmful factors
If gemcitabine is used to deplete Treg population, then immunosuppressive environment is reduced, but the effect on overall treatment efficacy is unclear
Solution Approach 1:
The patent implements feedback monitoring by measuring Treg population levels at baseline and after gemcitabine treatment. This feedback information, combined with measurements of MDSCs and effector T cells, allows prediction of whether the reduction in immunosuppression will translate to treatment efficacy, resolving the uncertainty about overall treatment outcome
Data Source
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AI summary
A method for predicting whether a patient will be a long-term survivor on treatment of a disease by adoptive cell transfer (ACT), is disclosed comprising: (i) analysing a blood-derived sample obtained from the patient for one or more prognostic markers of long-term survival on treatment of a disease by ACT, and; (ii) based on the analysis of step (i), predicting whether the patient will be a long-term survivor on treatment of the disease by ACT, wherein the disease is preferably a disease caused or exacerbated by infection with Epstein-Barr virus (EBV), such as EBV-positive nasopharyngeal carcinoma (NPC). Also disclosed are methods for treating a patient by ACT, methods for selecting a patient for treatment by ACT, and methods for selecting a patient for treatment of a disease by ACT, preferably EBV-positive NPC.