Dual-Specific CAR T Cells for Solid Tumor Expansion
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Solution Overview
Problem
Current CAR T cell therapy is effective for treating blood cancers but struggles to maintain long-term presence in patients, limiting its efficacy for solid tumors, necessitating improved methods to enhance CAR T cell expansion and persistence.
Innovation Solution
Genetically modified T cells equipped with two antigen binding domains: a first domain for expanding CAR T cells by binding to B cells and a second domain for targeting tumor cells, allowing for enhanced persistence and anti-tumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If CAR T cells are used to treat solid tumors, then anti-tumor activity is achieved, but long-term maintenance of CAR T cells in patients is insufficient
Solution Approach 1:
The CAR molecule is segmented into two distinct antigen binding domains: a first domain (e.g., anti-CD19) for expansion and a second domain (e.g., anti-tumor antigen) for anti-tumor activity. This segmentation allows the CAR T cell to sequentially achieve expansion followed by sustained anti-tumor function, resolving the contradiction between duration and reliability.
Solution Approach 2:
The dual-specific CAR molecule performs multiple functions: it enables expansion of CAR T cells through the first antigen binding domain while simultaneously providing anti-tumor activity through the second domain. This multi-functionality ensures both long-term maintenance and reliable efficacy for solid tumor treatment.
2Productivity
If CAR T cells are expanded timely in patients using B cells as targets, then potency and longevity of CAR T cells increase, but the complexity of the therapy increases
Solution Approach 1:
Two separate CAR molecules with different specificities are merged into a single dual-specific CAR molecule. This combining approach achieves the expansion function (via B cell targeting) and the anti-tumor function (via tumor antigen targeting) in one integrated construct, reducing the complexity of administering and managing multiple separate therapies while maintaining high productivity in CAR T cell expansion.
Data Source
AI summary
The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion in vivo and/or in vitro. For example, a cell may comprise a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR may recognize a surface molecule of a blood cell.