Allogeneic T Cell Line Selection for HLA-Matched Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for adoptive immunotherapy using donor-derived virus-specific T-cells are limited by the lack of timely availability and inefficacy, particularly in cases where seronegative and cord blood donors are unavailable, necessitating a method to select allogeneic T cell lines with high and consistent efficacy.
Innovation Solution
A method for selecting allogeneic T cell lines by utilizing a representation that identifies HLA alleles and their relative activities or frequencies, ensuring the selected T cell lines recognize immunodominant epitopes shared with the patient, thereby enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If donor-derived virus-specific T-cells are used for adoptive immunotherapy, then therapeutic efficacy is improved, but timely availability is limited
Solution Approach 1:
The patent applies preliminary action by pre-expanding and bank T-cell lines from healthy donors before they are needed for therapy. T-cell lines specific for viral epitopes (such as CMV, EBV, adenovirus) are generated in advance, characterized for their HLA restrictions and antiviral activity, and stored in a bank for rapid deployment when clinically needed, eliminating the time-consuming process of generating T-cells de novo for each patient
Solution Approach 2:
The patent segments the T-cell repertoire by generating separate T-cell lines specific for individual viral epitopes and restricted to specific HLA alleles. This segmentation allows the bank to store multiple specialized T-cell lines that can be selectively matched to patients based on their HLA type and viral infection status, improving both availability and efficacy
2Adaptability or versatility
If seronegative and cord blood donors are used, then donor availability is improved, but therapeutic efficacy deteriorates
Solution Approach 1:
The patent uses seropositive donors as proxies or 'copies' to generate T-cell lines that can be used to treat seronegative patients. By exposing seropositive donors to viral antigens and generating T-cell lines specific for conserved viral epitopes, the patent creates off-the-shelf T-cell products that can be administered to seronegative patients who lack pre-existing immunity, effectively copying the protective effect of viral exposure without requiring the patients themselves to be seropositive
3Ease of operation
If allogeneic T cell lines are selected without HLA matching, then selection process is simplified, but therapeutic efficacy decreases
Solution Approach 1:
The patent applies preliminary action by pre-characterizing T-cell lines for their HLA restrictions before banking. Each T-cell line is tested to determine which HLA alleles it requires for recognition of viral epitopes. This preliminary HLA typing and characterization data is stored in the bank database, allowing rapid HLA-matched selection for each patient without requiring complex matching procedures at the time of therapy
Solution Approach 2:
The patent implements feedback by using patient HLA typing results to guide selection of appropriate T-cell lines from the bank. The system takes feedback from the patient's HLA genotype and uses it to select T-cell lines with matching HLA restrictions, ensuring optimal recognition and efficacy while maintaining a streamlined selection process
Data Source
AI summary
Disclosed herein are methods of selecting an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer. Also disclosed are methods of selecting a donor from whom to derive an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer.