Chimeric Receptor T-Cell Dosing Using Tumor Microenvironment Profiles
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Solution Overview
Problem
Cancer cells employ mechanisms to evade immune targeting by T and B lymphocytes, limiting the effectiveness of human T cell therapies.
Innovation Solution
Characterize the tumor microenvironment (TME) using gene expression profiling and intratumoral T cell density to determine an effective dose of chimeric receptors for T cells, optimizing treatment outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cells are engineered to express chimeric antigen receptors to target cancer cells, then the ability to specifically target and kill cancer cells is improved, but cancer cells employ mechanisms to prevent immune cells from successfully targeting them, reducing treatment effectiveness
Solution Approach 1:
The patent analyzes the tumor microenvironment using gene expression profiling to identify specific parameters such as T cell density, immune suppression markers, and inflammatory factors. Based on these parameter assessments, the dosage and composition of CAR-T cells are customized for each patient, transforming a one-size-fits-all approach into a personalized treatment strategy that adapts to the specific biological parameters of each tumor microenvironment
Solution Approach 2:
The patent performs preliminary characterization of the tumor microenvironment through gene expression analysis before administering CAR-T cell therapy. This preliminary action identifies patients who are most likely to respond to treatment by assessing T cell density, immune suppression markers, and other microenvironmental factors, allowing for patient selection and dosage optimization before the actual treatment begins
2Ease of operation
If a standardized dose of CAR-T cells is administered to all patients, then the treatment process is simplified, but individual patient responses vary significantly due to differences in tumor microenvironment characteristics
Solution Approach 1:
The patent applies local quality by customizing the CAR-T cell dosage and composition based on each patient's specific tumor microenvironment characteristics. Rather than applying a uniform treatment protocol, the treatment is tailored to the local biological conditions of each patient's tumor, including T cell density, immune suppression markers, and inflammatory factor levels, thereby optimizing efficacy for each individual case
3Reliability
If the dosage of CAR-T cells is increased to overcome cancer cell evasion mechanisms, then the ability to kill cancer cells is improved, but the risk of adverse effects and treatment toxicity increases
Solution Approach 1:
The patent uses gene expression profiling to measure specific parameters of the tumor microenvironment, such as T cell density and immune suppression markers. Based on these parameter measurements, the CAR-T cell dosage is precisely adjusted - neither too high to cause excessive toxicity nor too low to be ineffective. This parameter-based dosing strategy optimizes the balance between therapeutic effectiveness and safety
Data Source
AI summary
The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric receptor (e.g., CAR or TCR) genetically modified T cell immunotherapy. Some aspects of the disclosure relate to methods of characterizing the pre-infusion tumor microenvironment and determining an effective dose of a T cell immunotherapy.