Chimeric Antigen Receptors Targeting T-Cell Malignancies
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Solution Overview
Problem
Current chimeric antigen receptor (CAR) therapies have limited success in targeting T-cell malignancies, which have poorer outcomes compared to B-cell malignancies, and there is a need for more effective, safe, and efficient targeting methods for T-cell associated hematologic malignancies.
Innovation Solution
Development of engineered chimeric antigen receptors (CARs) with specific antigen recognition domains such as CD2, CD3, CD4, CD5, CD7, and CD8, combined with co-stimulatory and signaling domains, for targeted immunotherapy, including the use of engineered cells expressing these CARs to selectively target and reduce T-cell leukemia and lymphoma cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR therapy is used, then B-cell malignancies show remarkable results with long-term remissions, but T-cell malignancies have dramatically poorer outcomes with limited success
Solution Approach 1:
The patent applies local quality by designing CARs with specific antigen recognition domains tailored to target different cell types. CD19 CARs are used for B-cell malignancies while CD5 CARs are used for T-cell malignancies, allowing each CAR to have optimized local properties for its specific target rather than using a universal approach
Solution Approach 2:
The patent employs parameter changes by modifying the antigen recognition domain of the CAR to target different antigens (CD19 vs CD5) expressed on different malignancy types. This parameter modification enables the therapy to adapt from treating B-cell malignancies to treating T-cell malignancies with improved efficacy
2Reliability
If anti-CD5 antibodies are used to treat T-cell leukemias, then treatment is attempted, but success is limited
Solution Approach 1:
The patent uses composite materials by creating chimeric antigen receptors that combine multiple functional domains: an extracellular antigen recognition domain (anti-CD5 scFv), a transmembrane domain, and intracellular signaling domains (CD3ζ, CD28, 4-1BB). This composite structure integrates antibody binding capability with T-cell activation signaling, creating a more effective therapy than simple anti-CD5 antibodies
Solution Approach 2:
The patent applies merging by combining the antigen recognition function of anti-CD5 antibodies with the signaling and co-stimulatory functions of T-cell receptors and co-stimulatory molecules into a single CAR construct. This unified structure enables both specific target recognition and potent T-cell activation in one integrated therapy
Data Source
AI summary
The present disclosure provides chimeric anti-gen receptor polypeptides having antigen recognition domains for CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens, and polynucleotides encoding for the same. The present disclosure also provides for engineered cells expressing the poly-nucleotide or polypeptides. In some embodiments, the disclosure provides methods for treating diseases associated with CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens.