HLA-Agnostic Immune Assay for CD8+ T Cell Monitoring
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Solution Overview
Problem
Traditional methods for monitoring peripheral immune responses to oncolytic viruses require large volumes of blood and cannot distinguish between CD8+ and CD4+ T cell responses, limiting their effectiveness in assessing anti-tumor activity.
Innovation Solution
Development of an HLA-agnostic immune assay using specific peptide pools corresponding to vaccinia virus epitopes to measure CD8+ T cell responses, allowing for the identification of patients responsive to oncolytic vaccinia virus treatment with reduced sample requirements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional overlapping peptide pools are used to cover the entire virus proteome, then comprehensive T cell response monitoring is achieved, but large volumes of blood are required which are not feasible to obtain
Solution Approach 1:
The patent extracts only the essential epitopic regions from the complete virus proteome. Instead of screening all possible peptides, the invention identifies and isolates specific MHC class I-restricted epitopes that are sufficient to monitor CD8+ T cell responses, thereby reducing the required blood volume while maintaining measurement effectiveness
Solution Approach 2:
The patent segments the virus proteome into discrete epitopic regions and organizes them into targeted peptide pools. By dividing the comprehensive proteome coverage into specific functional segments (epitope pools organized by MHC supertypes), the assay can monitor T cell responses using fewer peptides and less blood sample
2Adaptability or versatility
If 15 amino-acid length peptides are used to track all T cell responses, then both CD4+ and CD8+ T cell responses can be monitored, but the delineation of CD8+ versus CD4+ responses is not possible
Solution Approach 1:
The patent applies local quality by designing peptide pools with specific properties tailored to detect CD8+ T cell responses. The epitopic peptides are selected and organized based on MHC class I restriction, creating localized functional characteristics in the assay that enable specific detection of CD8+ responses rather than generic T cell responses
Solution Approach 2:
The patent changes the peptide length parameter from the traditional 15 amino acids to shorter epitopic sequences (typically 8-11 amino acids) that are characteristic of MHC class I-restricted CD8+ T cell epitopes. This parameter change, combined with organizing peptides into MHC supertype pools, enables specific delineation of CD8+ responses
3Measurement precision
If the entire peptide set is screened to monitor peripheral immune response, then complete immune repertoire assessment is achieved, but the complexity and sample requirements become impractical
Solution Approach 1:
The patent applies partial action by screening a selected subset of epitopic peptides rather than the entire virus proteome. The invention identifies that monitoring responses to specific MHC class I-restricted epitopes is sufficient to assess anti-tumor immune activity, eliminating the need to screen all possible peptides while maintaining clinical relevance
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The assay effectively tracks CD8+ T cell responses with minimal sample volume, differentiating between responders and non-responders, and correlates with disease status and treatment outcome, enhancing the monitoring of anti-tumor immune responses.
Implementation Method 1
using one or more predetermined pools of peptides, wherein each peptide corresponds to an MCH class 1-restricted vaccinia virus epitope
Implementation Method 2
measuring a cytokine production by the PBMCs
Data Source
AI summary
Provided herein are methods and compositions for assaying vaccinia virus-specific T cell responses in a sample from a subject undergoing treatment with an oncolytic vaccinia virus. The compositions comprise custom peptide pools from known immunogenic vaccinia virus epitopes in an HLA-agnostic format to profile peripheral CD8+T cell responses.