Allogeneic CAR T Cell Engineering for Relapsed Cancer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current CAR T cell therapies for cancer are limited by the expression of endogenous T cell receptors, which can lead to graft-versus-host disease and require autologous approaches that are time and cost intensive, and have limited efficacy with high relapse rates.
Innovation Solution
Development of allogeneic CAR T cells with reduced or no detectable expression of endogenous T cell receptors, administered with a lymphodepletion regimen to reduce cancer cell burden and enhance immune cell expansion and persistence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If allogeneic CAR T cells are used, then treatment time and cost are reduced, but graft-versus-host disease risk increases
Solution Approach 1:
The patent removes the harmful endogenous T cell receptor from the CAR T cell product through genetic manipulation (e.g., CRISPR/Cas9-mediated deletion of TRAC and TRBC genes), extracting the problematic component while preserving the therapeutic CAR functionality. This allows allogeneic cells to be used without triggering graft-versus-host disease.
Solution Approach 2:
The patent converts the potential harm of endogenous T cell receptor expression into a benefit by using the same genetic editing tools to create a more controlled and safer product. The genetic manipulation that eliminates GvHD risk also enables better manufacturing standardization and quality control of allogeneic products.
2Object-affected harmful factors
If autologous CAR T cells are used, then graft-versus-host disease is prevented, but treatment time and cost increase
Solution Approach 1:
The patent prepares allogeneic CAR T cells in advance from healthy donor pools, performing genetic editing and expansion before patient need arises. This preliminary action eliminates the time-consuming process of collecting, processing, and manufacturing patient-specific cells while maintaining safety through pre-validated genetic modifications.
Solution Approach 2:
The patent creates standardized allogeneic CAR T cell products that can be copied and distributed to multiple patients without customization. These pre-manufactured cells serve as templates that can be rapidly deployed to multiple patients, dramatically reducing treatment time and manufacturing cost compared to patient-specific autologous products.
3Duration of action of moving object
If lymphodepletion regimen is administered, then CAR T cell expansion and persistence are enhanced, but cancer cell burden increases temporarily
Solution Approach 1:
The patent employs a structured lymphodepletion regimen with specific timing and dosing schedules (e.g., fludarabine for 5 days followed by cyclophosphamide for 2 days) that creates temporary immune suppression to facilitate CAR T cell engraftment, followed by natural immune recovery that helps control cancer cells after the therapeutic cells are established.
Solution Approach 2:
The lymphodepletion regimen is administered in advance of CAR T cell infusion to pre-condition the patient's immune system, creating space and reducing competition for the incoming therapeutic cells. This preliminary action ensures optimal conditions for CAR T cell expansion and persistence while the regimen's effects are transient and manageable.
Data Source
AI summary
The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, used in populations of subjects having cancer who previously received an autologous cell therapy, had a response, and subsequently relapsed.