CD19 CAR Immune Cell Therapy for Durable Autoimmune B-Cell Control
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Solution Overview
Problem
Current treatments for autoimmune diseases like lupus and rheumatoid arthritis, such as high-dose corticosteroids and monoclonal antibodies, are inadequate and often lead to resistance, necessitating frequent administrations and lacking a durable therapeutic effect.
Innovation Solution
Administration of low-dose engineered immune cells, such as CAR-T cells and CAR-NK cells, targeting CD19 antigens, which are modified to include a chimeric antigen receptor (CAR) and optimized for reduced immunogenicity, administered at lower doses than those used for B cell malignancies, optionally with lymphodepletion and CRISPR-mediated genome modifications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high-dose corticosteroids are administered to achieve general immunosuppression, then autoimmune disease symptoms are suppressed, but patient tolerance deteriorates and resistance develops over time
Solution Approach 1:
The invention segments the immune system into specific target cells (CD19+ B cells) rather than suppressing the entire immune system. CAR-T cells are engineered to specifically recognize and eliminate CD19-expressing B cells, achieving disease control while preserving overall immune function and reducing systemic side effects compared to broad immunosuppression with corticosteroids
Solution Approach 2:
The CAR-T cells are engineered to be self-sustaining and self-replicating within the patient's body. Once administered, these modified T cells persist and continuously patrol for CD19+ B cells, providing long-term disease control without requiring repeated high-dose administrations, thereby avoiding resistance development
2Reliability
If monoclonal antibodies are administered weekly to target B cells, then symptom management is achieved, but treatment complexity increases and duration of action decreases
Solution Approach 1:
The CAR-T cells are engineered to be self-sustaining and self-replicating within the patient's body. Once administered, these modified T cells persist and continuously patrol for CD19+ B cells, providing long-term disease control without requiring repeated high-dose administrations, thereby avoiding resistance development
Solution Approach 2:
The CAR-T cells provide continuous therapeutic action by permanently residing in the patient's immune system. Unlike monoclonal antibodies that require weekly infusions, the engineered T cells continuously monitor and eliminate CD19+ B cells over extended periods, achieving sustained symptom management with single or infrequent administrations
3Reliability
If standard CAR-T cell doses are used to treat autoimmune diseases, then B cell targeting is achieved, but treatment safety deteriorates due to excessive immune suppression
Solution Approach 1:
The invention fundamentally changes the dosage parameter from standard cancer treatment levels to much lower levels appropriate for autoimmune disease. The patent specifies administering approximately 10^4 to 10^6 CAR-T cells, which is 100-1000 times lower than doses used for B cell malignancies, achieving adequate B cell control while minimizing harmful immune suppression
Solution Approach 2:
The treatment achieves localized targeting of pathogenic B cells without causing systemic immune collapse. The low-dose CAR-T cells specifically eliminate CD19+ B cells responsible for autoimmune pathology while preserving other immune cell populations and functions, creating a targeted therapeutic effect with minimal off-target harm
Data Source
AI summary
The invention comprises methods and compositions for treating autoimmune diseases with engineered immune cells including cytotoxic T cells and natural killer (NK) cells. The engineered immune cells comprise a chimeric antigen receptor (CAR). Methods of making the engineered cells, methods of administration and treatment regimens are also disclosed.