BCMA CAR Immune Cells for Selective Autoimmune B-Cell Depletion
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Solution Overview
Problem
Current treatments for autoimmune diseases like lupus, rheumatoid arthritis, and multiple sclerosis are inadequate, requiring frequent administration and often result in severe side effects due to immunosuppression, necessitating a more effective and safer therapeutic approach.
Innovation Solution
Administering BCMA-targeting engineered immune cells, such as CAR-T cells or CAR-NK cells, which are armored to avoid host immune system destruction, allowing for lower doses and reduced side effects while effectively targeting mature B cells responsible for autoimmune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibody therapies (e.g., Rituximab) are used to treat autoimmune diseases, then B cell depletion is achieved, but frequent weekly intravenous administrations are required and resistance develops over time
Solution Approach 1:
The engineered immune cells are designed to self-renew and persist in the patient's body, continuously depleting B cells without requiring frequent external administrations. The cells serve themselves by maintaining their own population and therapeutic function long-term
Solution Approach 2:
The patent changes the fundamental parameter from transient antibody molecules requiring repeated dosing to persistent engineered cells that provide sustained therapy. This transforms the treatment from frequent short-acting interventions to infrequent long-acting cell-based therapy
2Object-affected harmful factors
If high-dose corticosteroids are used for general immunosuppression, then autoimmune symptoms are suppressed, but severe side effects occur
Solution Approach 1:
The engineered immune cells provide localized, targeted immunosuppression specifically against B cells involved in autoimmune responses, rather than global immunosuppression. This selective action spares other immune functions and reduces systemic side effects
Solution Approach 2:
The patent uses engineered immune cells as intermediary agents that mediate the suppression of autoimmune B cells. These cells act as a controlled bridge between the therapeutic goal (B cell depletion) and the patient's immune system, avoiding the need for harsh direct immunosuppression
3Object-affected harmful factors
If anti-CD19 or anti-CD20 antibody therapies are used to deplete B cells, then autoimmune responses are reduced, but severe side effects occur including PML and Hepatitis B reactivation
Solution Approach 1:
The engineered immune cells provide localized, targeted depletion of pathogenic B cells through direct cell-cell contact and cytotoxic mechanisms, rather than systemic antibody-mediated depletion. This targeted approach spares other immune components and reduces severe side effects
Solution Approach 2:
The patent uses engineered immune cells that copy and enhance the body's natural immune surveillance and elimination mechanisms, rather than introducing external antibodies. These engineered cells behave more like native immune cells, reducing immunogenicity and severe adverse reactions
Data Source
AI summary
The invention comprises methods and compositions for treating autoimmune diseases with BCMA-targeting engineered immune cells including T cells and natural killer (NK) cells. The engineered immune cells comprise an anti-BCMA chimeric antigen receptor (CAR). Methods of making the engineered cells, methods of administration, and treatment regimens are also disclosed.