CAR T Cells Targeting CD83 for Autoimmune Therapy
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Solution Overview
Problem
Current treatments for autoimmune diseases like systemic lupus erythematosus (SLE) are limited, with glucocorticoids causing broad immunosuppression and side effects, and biologic therapeutics have largely failed to provide effective alternatives for steroid-refractory cases.
Innovation Solution
Genetically modified immune cells expressing chimeric antigen receptors (CARs) targeting CD83 and optionally CD19 are administered to suppress autoreactive lymphocytes, allowing for selective inhibition of autoreactive cells while minimizing off-target effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucocorticoids are used to treat autoimmune diseases, then immunosuppression is achieved, but broad immunosuppression increases the risk for opportunistic infections and causes side effects
Solution Approach 1:
The patent segments the immune system targeting approach by using CAR T cells that specifically recognize and bind to autoreactive B cells expressing CD19 and CD83. This segmentation allows selective suppression of only the harmful autoreactive subset rather than broad immunosuppression of the entire immune system, thereby maintaining efficacy while reducing harmful side effects and infection risk.
2Adaptability or versatility
If biologic therapeutics are tested in SLE, then alternative treatment options are sought, but attempts have largely failed to provide effective alternatives
Solution Approach 1:
The patent introduces CAR T cells as an intermediary therapeutic agent that bridges the gap between conventional treatments and the need for targeted therapy. These genetically modified T cells serve as living mediators that specifically recognize autoreactive B cells through dual CAR expression (anti-CD19 and anti-CD83), providing a reliable and effective treatment alternative that has not been achieved by previous biologic therapeutics.
3Measurement precision
If immune cells expressing anti-CD83 CAR are administered, then selective targeting of autoreactive lymphocytes is achieved, but treatment specificity must be maintained to avoid off-target effects
Solution Approach 1:
The patent merges two CAR targeting systems into a single T cell product: one CAR targets CD19 (present on B cells) and the other targets CD83 (present on activated lymphocytes including autoreactive B cells). The dual CAR configuration ensures that T cells require co-expression of both CARs to achieve optimal targeting, thereby maintaining high specificity for autoreactive B cells while minimizing off-target effects on non-autoreactive cells.
Data Source
AI summary
Disclosed are compositions and methods for treating autoimmune diseases such as lupus, including immune cells expressing at least a chimeric antigen receptor (CAR) polypeptides that binds CD83 and uses thereof for suppressing and/or killing autoreactive cells in a subject having an autoimmune disease.