TRM Cell Gene Expression Profiles for Cancer Immunotherapy
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Solution Overview
Problem
The molecular characteristics driving the efficient immune response of tissue-resident memory T (TRM) cells in cancer patients are poorly understood, hindering their identification and therapeutic harnessing for effective cancer treatment.
Innovation Solution
Administering a population of T-cells with altered expression of specific genes, such as TIM3, CXCL13, and CD39, or using agents that induce these expressions, to enhance anti-tumor responses, and employing diagnostic methods to identify subjects likely to benefit from cancer treatments based on TRM cell populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tissue-resident memory T (TRM) cells are administered to treat cancer, then anti-tumor response is enhanced, but the molecular characteristics driving their efficient immune response are poorly understood
Solution Approach 1:
The patent identifies and measures specific molecular parameters (gene expression levels of TIM3, CXCL13, CD39, and other markers) in TRM cells to characterize their functional state. By establishing baseline expression levels and comparing them across different patient groups and treatment responses, the patent transforms the unknown molecular characteristics into measurable parameters that can guide therapy selection and optimization.
2Reliability
If TRM cell populations are used for targeted cancer treatment, then clinical outcomes are improved, but identification of subjects likely to benefit is challenging
Solution Approach 1:
The patent establishes specific molecular parameter thresholds (expression levels of TIM3, CXCL13, CD39, and combination markers) that predict treatment response. By measuring these parameters in patient samples and comparing against established baselines, clinicians can identify subjects likely to benefit from TRM cell therapy, transforming the difficult subject identification process into a measurable diagnostic task.
Solution Approach 2:
The patent creates a feedback loop where molecular characteristics of TRM cells are measured, compared to baseline values, and used to predict treatment outcomes. This feedback mechanism allows for selection of appropriate candidates and potential optimization of therapy based on the measured molecular profile of the patient's TRM cells.
3Reliability
If genes such as TIM3, CXCL13, and CD39 are modified to enhance TRM cell function, then anti-tumor response is improved, but the complexity of molecular manipulation increases
Solution Approach 1:
The patent focuses on modifying specific molecular parameters (gene expression levels) rather than undertaking complex structural changes to the cells. By targeting expression levels of identified markers like TIM3, CXCL13, and CD39, the approach simplifies the manipulation complexity while achieving enhanced anti-tumor function through regulated expression of these key molecules.
Data Source
AI summary
This disclosure provides methods of treating cancer or eliciting an anti-tumor response in a subject by administering an effective amount of a population of T-cells that exhibits higher or lower than baseline expression of one or more genes. In other aspects, methods are provided to diagnose cancer and determine prognosis of cancer patients. Also provided are methods to identify the antigens or antigen receptors associated with the isolated and/or purified cell populations that elicit a more positive prognosis.