Therapeutic T Cell Isolation via Neoantigen-Specific APCs
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Solution Overview
Problem
Current methods for isolating and expanding tumor-infiltrating lymphocytes (TILs) that target tumor-associated antigens in breast cancer patients are inefficient due to unknown targets and the complexity of isolating tumor-reactive T cells, which hinders the effectiveness of T cell-based immune therapy.
Innovation Solution
A method involving the generation of patient-specific omics data from tumor and normal tissues to identify tumor-specific neoantigens, followed by the use of recombinant antigen-presenting cells to activate and expand T cells that react to these neoantigens, potentially supplemented with immunostimulatory cytokines and checkpoint inhibitors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional methods are used to isolate and expand tumor-infiltrating lymphocytes, then the process is simpler, but the efficiency and effectiveness of isolating tumor-reactive T cells is low
Solution Approach 1:
The patent performs preliminary identification of tumor-specific neoantigens through omics data analysis and sequencing before the T cell isolation process. This preliminary characterization of tumor antigens allows for targeted isolation of T cells that specifically recognize these neoantigens, significantly improving isolation efficiency without requiring complex iterative screening processes
Solution Approach 2:
The patent uses recombinant antigen-presenting cells as an intermediary to bridge the tumor neoantigens and patient T cells. These engineered APCs present the identified neoantigens to T cells, enabling selective activation and expansion of tumor-reactive T cells. This intermediary approach simplifies the isolation process while maintaining high specificity and effectiveness
2Productivity
If the targets of TILs are unknown, then the isolation process becomes more difficult, but using known targets may reduce versatility for different patients
Solution Approach 1:
The patent segments the tumor antigen landscape into patient-specific neoantigens identified through individualized omics data analysis. By breaking down the complex tumor antigen repertoire into discrete, identifiable neoantigens for each patient, the method enables targeted isolation of T cells against specific tumor targets while maintaining the ability to customize the approach for different patients based on their unique tumor mutational profiles
Solution Approach 2:
The patent changes the key parameter from using generic or unknown T cell targets to using precisely identified patient-specific neoantigens. Through sequencing and bioinformatics analysis, the method determines the specific neoantigen profile for each patient's tumor, allowing customization of the T cell isolation and expansion process to match each patient's unique tumor characteristics
Data Source
AI summary
Therapeutic T cells can be prepared from a population of TILs (tumor infiltrating lymphocytes) using tumor and patient-specific neoantigens expressed in antigen presenting cells to select for tumor reactive T cells. Selected tumor reactive T cells are then expanded and administered to the patient.