Peripheral Blood T Cell Isolation for Cancer-Specific TCR Selection
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Solution Overview
Problem
Existing methods face challenges in identifying and isolating T cells and TCRs that specifically recognize cancer antigens, making it difficult to implement adoptive cell therapy effectively for widespread cancer treatment.
Innovation Solution
A method involving the selection and enrichment of PD-1 expressing T cells from peripheral blood mononuclear cells, co-culturing them with autologous antigen-presenting cells presenting cancer-specific mutated amino acid sequences, and selecting T cells with antigenic specificity for these sequences, allowing for the isolation of TCRs with personalized antigen recognition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If current methods are used to obtain cancer-reactive T cells and TCRs, then T cells can be isolated, but the process is invasive and time-consuming
Solution Approach 1:
The patent uses antigen-presenting cells (APCs) as intermediaries to present cancer-specific mutated amino acid sequences to T cells. This mediator approach enables indirect identification and isolation of cancer-reactive T cells through their interaction with APCs displaying tumor-specific antigens, avoiding direct invasive sampling while maintaining isolation efficiency
Solution Approach 2:
The patent replaces invasive mechanical procedures (such as surgical biopsy or direct tumor sampling) with an in vitro co-culture system. By substituting mechanical invasion with biochemical interactions in culture, the method achieves T cell isolation without invasive procedures while preserving productivity through scalable cell culture techniques
2Productivity
If current methods are used to obtain cancer-reactive T cells and TCRs, then T cells can be isolated, but the process is time-consuming
Solution Approach 1:
The patent performs preliminary identification of cancer-specific mutations and prepares antigen-presenting cells with mutated amino acid sequences before T cell isolation. This preliminary action includes sequencing tumor DNA, identifying mutations, and pre-loading APCs with tumor antigens, which accelerates the subsequent T cell isolation process by eliminating sequential delays
Solution Approach 2:
The patent combines multiple steps into a single co-culture process: APCs presenting tumor antigens and T cells are cultured together in one system, allowing simultaneous antigen presentation, T cell activation, and enrichment of cancer-reactive T cells. This merging of steps reduces the overall time required compared to sequential procedures
3Quantity of substance
If T cells are selected from bulk peripheral blood, then T cells can be obtained, but cancer-reactive T cells are difficult to identify and isolate
Solution Approach 1:
The patent applies local quality by creating a selective microenvironment in the co-culture system where only T cells with specificity for cancer-specific mutated amino acid sequences are activated and enriched. The APCs present tumor-specific antigens locally, ensuring that only the relevant T cell subset responds, thereby achieving high specificity while maintaining adequate quantity
Solution Approach 2:
The patent changes the selection parameter from general T cell markers to cancer-specific antigen recognition. By using APCs presenting mutated amino acid sequences as the selection criterion, the method transforms the selection process to enrich for T cells with precise cancer antigen specificity while obtaining sufficient numbers for therapy
Data Source
AI summary
Disclosed are methods of isolating T cells and TCRs having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.