ROR-1 CAR Architecture for Specific and Effective Cell Targeting
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Solution Overview
Problem
Current chimeric antigen receptors (CARs) for treating diseases such as cancers and autoimmune disorders have limitations in efficacy and specificity, particularly in targeting the ROR-1 antigen, leading to suboptimal therapeutic outcomes.
Innovation Solution
Development of a chimeric antigen receptor (CAR) comprising a ROR-1 antigen binding domain, a spacer, a transmembrane domain, a costimulatory signaling domain (4-1BB or CD28), and a CD3 zeta signaling domain, integrated into immune effector cells, with optional inclusion of a cell tag and cytokine like IL-15, and controlled by gene switch polypeptides for ligand-inducible expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CARs are used for treating cancers and autoimmune disorders, then treatment is provided, but efficacy and specificity are insufficient
Solution Approach 1:
The patent modifies the CAR structure by changing parameters such as incorporating costimulatory signaling domains (CD28, 4-1BB, OX40) and optimizing spacer lengths to enhance both the specificity and efficacy of ROR-1 targeted immune cell therapy
Solution Approach 2:
The invention uses composite CAR designs combining multiple signaling domains (CD3 zeta, costimulatory domains like CD28 and 4-1BB) to create a multi-functional receptor that simultaneously improves targeting specificity and therapeutic efficacy
Data Source
AI summary
Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-ROR-1 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.