Immuno-activatable CAR T Cells Targeting Age-associated B Cells
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Solution Overview
Problem
Current treatments for autoimmune diseases, particularly those involving age-associated B cells, are inadequate in managing the specific contribution of these cells to disease pathology, leading to an unmet need for effective management strategies.
Innovation Solution
Development of immuno-activatable cells equipped with first and second chimeric antigen receptors that target CD11c+Tbet+ B cells, specifically designed to bind with low affinity and stimulate an immune response, thereby reducing the number of age-associated B cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive drugs are used to treat autoimmune diseases, then general immune suppression is achieved, but specific management of age-associated B cells remains inadequate
Solution Approach 1:
The invention divides the immune system into specific targetable components by identifying and isolating age-associated B cells through unique marker combinations (CD11c+, Tbet+, CD38+, CD27+), allowing targeted intervention rather than general immunosuppression
Solution Approach 2:
The patent uses chimeric antigen receptors (CARs) as intermediary structures that bridge the gap between immune cells and specific B cell targets. These CARs contain antigen-binding domains that specifically recognize B cell markers, enabling precise targeting without broad immunosuppression
2Force
If chimeric antigen receptors with high affinity binding are used, then strong immune activation occurs, but risk of off-target effects increases
Solution Approach 1:
The invention applies different binding affinities to different antigen targets: high affinity for CD19 (to ensure strong activation) and low affinity for CD11c (to reduce off-target effects). This localized differentiation of binding strength allows selective targeting of age-associated B cells while sparing other cell types
Solution Approach 2:
The patent systematically varies the affinity parameter of CAR-antigen interactions by selecting antibodies with different binding characteristics. This parameter optimization enables tuning of the immune response to achieve therapeutic efficacy while minimizing toxicity
3Measurement precision
If multiple chimeric antigen receptors are expressed on a single cell, then targeting specificity increases, but cell complexity increases
Solution Approach 1:
The invention merges multiple CAR expression cassettes into single viral vectors or nucleic acid constructs, allowing simultaneous delivery of multiple CAR genes to a single T cell. This consolidation reduces the complexity of the delivery system while maintaining the dual-targeting capability
Solution Approach 2:
The patent creates universal CAR constructs that can be combined in different configurations to target various B cell markers. These multi-functional CAR designs allow a single cell type (T cell) to perform multiple targeting functions through expression of different CAR combinations
Data Source
AI summary
This document relates to methods and materials for treating a mammal having an autoimmune disease. For example, materials and methods for producing an immuno-activatable cell comprising a first chimeric antigen receptor and a second chimeric antigen receptor are provided. Methods and materials for treating a mammal having an autoimmune disease comprising administering an immuno-activatable cell are also provided.