CAR-Modified T Regulatory Cells for Type 1 Diabetes Autoimmunity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for type 1 diabetes primarily manage symptoms through insulin administration and blood glucose monitoring, but do not address the underlying autoimmune response, requiring constant and painful interventions.
Innovation Solution
Development of modified regulatory T cells equipped with chimeric antigen receptors (CARs) specific for dipeptidyl peptidase-like protein 6 (DPP6) or fibroblast activation protein (FAP), which can suppress autoimmune responses and potentially reverse β-cell loss.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (insulin administration and blood glucose monitoring) are used, then blood glucose levels can be managed, but the underlying autoimmune response is not addressed and constant painful interventions are required
Solution Approach 1:
The patent employs autologous T regulatory cells that are modified ex vivo and then reinfused into the patient. These modified cells autonomously recognize and suppress autoimmune responses against pancreatic beta cells through their engineered CAR receptors, eliminating the need for continuous external intervention such as insulin injections and blood glucose monitoring. The immune system essentially treats itself with the help of the engineered regulatory cells.
Solution Approach 2:
The treatment involves extracting T regulatory cells from the patient, modifying them with CAR constructs specific to pancreatic beta cell antigens (such as insulin, GAD65, or IA-2), and expanding them ex vivo before reinfusion. This preliminary engineering of the cells allows them to be pre-programmed with the ability to specifically suppress autoimmune responses, rather than waiting for the autoimmune damage to occur and then managing symptoms.
2Duration of action of stationary object
If conventional treatments are used, then lifelong management is achieved, but the number of β-islet cells continues to decrease until all cells are lost
Solution Approach 1:
The patent harnesses the patient's own immune system, which is normally causing harm through autoimmune attack on beta cells, and redirects it to provide protection. By engineering T regulatory cells with CAR receptors specific to beta cell antigens, the same immune system that is destroying beta cells is converted into a protective force that suppresses the autoimmune response and preserves remaining beta cell mass.
Solution Approach 2:
The modified T regulatory cells act as intermediaries between the immune system and the pancreatic beta cells. These cells express CAR receptors that specifically recognize beta cell antigens, allowing them to intercept and suppress autoimmune responses before they can damage the beta cells, thereby serving as a protective mediator layer.
3Reliability
If CAR-modified T cells are administered, then autoimmune responses can be suppressed and β-cell loss potentially reversed, but the treatment complexity increases
Solution Approach 1:
The treatment process is segmented into distinct phases: (1) extraction and isolation of T regulatory cells from patient blood, (2) genetic modification to introduce CAR constructs, (3) ex vivo expansion of modified cells, (4) quality control and characterization, and (5) reinfusion into the patient. This segmentation allows each step to be optimized and controlled independently, managing the overall complexity.
Solution Approach 2:
The patent replaces the need for continuous mechanical interventions (insulin injections, blood sampling) with a biological system (engineered T regulatory cells) that provides sustained therapeutic effect. This substitution transitions from a mechanical treatment approach to a regenerative biological approach.
Data Source
AI summary
The present invention includes compositions and methods for an DPP6 specific chimeric antigen receptor (CAR). In certain embodiments the DPP6 specific CAR is expressed on a T regulatory cell. In certain embodiments, the DPP6 specific CAR is used to treat type 1 diabetes.