Adaptive Immune Receptor Sequencing for Immunocompetence Stratification
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Solution Overview
Problem
Current methods lack a detailed understanding of a patient's immunological status, which is crucial for designing effective immunotherapy regimens, particularly in cancer treatment, hematopoietic cell transplants, and solid organ transplants, and for optimizing responses to vaccines, due to the cytotoxic effects of conventional therapies on the adaptive immune system.
Innovation Solution
A method for determining immunological status by quantifying adaptive immune receptor (AIR) sequence diversity and distribution through nucleic acid sequencing, using multiplex PCR and high-throughput sequencing to assess TCR and IG repertoire diversity and clonality, enabling prediction of immunotherapy responses and potential side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cytotoxic therapies are used to treat cancer, then tumor cells are killed, but the adaptive immune system is damaged and loses diversity
Solution Approach 1:
The patent performs adaptive immune receptor sequencing before immunotherapy administration to establish a baseline of immune diversity and identify patients at risk for severe immune-mediated adverse events. This preliminary assessment allows for risk stratification and proactive management of immune toxicity before it occurs.
Solution Approach 2:
The patent implements continuous monitoring of adaptive immune receptor sequences during and after immunotherapy to detect clonal expansions and immune-mediated adverse events. This feedback mechanism enables real-time adjustment of therapy dosage or interruption to prevent severe immune toxicity while maintaining treatment effectiveness.
2Reliability
If immunotherapy is administered to patients with compromised immune systems, then cancer treatment can be effective, but the risk of severe immune-mediated adverse events increases
Solution Approach 1:
The patent assesses adaptive immune receptor diversity before initiating immunotherapy to identify patients with compromised immune systems who are at high risk for severe immune-mediated adverse events. This baseline characterization enables risk stratification and proactive management strategies.
Solution Approach 2:
The patent continuously monitors adaptive immune receptor sequences during immunotherapy to detect clonal expansions and immune-mediated adverse events, enabling real-time adjustment of therapy dosage or interruption to prevent severe adverse events while maintaining treatment effectiveness.
3Measurement precision
If detailed immunological assessment is performed using high-throughput sequencing, then immunocompetence can be precisely characterized, but the complexity and cost of the methodology increases
Solution Approach 1:
The patent focuses sequencing efforts on specific adaptive immune receptor regions (such as CDR3 segments) rather than performing complete genome sequencing. This segmentation approach maintains high measurement precision for immunocompetence assessment while significantly reducing the complexity and cost of the methodology.
Solution Approach 2:
The patent develops a multi-functional sequencing platform that can assess multiple aspects of immunocompetence including diversity, clonality, and functional status of adaptive immune receptors. This universal approach consolidates multiple assessment functions into a single methodology, reducing overall complexity while maintaining comprehensive precision.
Data Source
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AI summary
Disclosed are methods for determining the immunological status of the adaptive immune system of a subject by identifying and quantifying rearranged DNA (and/or subsequently transcribed RNA) sequences encoding T cell receptor (TCR) and/or immunoglobulin (IG) polypeptides, in a lymphoid DNA-containing sample from the subject. TCR and/or IG sequence diversity and sequence distribution permit immunocompetence and immune repertoire assessment and reflect the degree of T cell or B cell clonality and clonal expansion in the sample. Methods for stratifying patient populations on the basis of immunocompetence including likelihood of responding to immunotherapy are also described.