CD123 CAR T Cells for AML Persistence
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Solution Overview
Problem
Current treatments for acute myeloid leukemia (AML), particularly relapsed or refractory AML, have limited effectiveness and poor prognosis, and existing CAR T cell therapies face challenges in persistence and efficacy when targeting AML cells.
Innovation Solution
Development of chimeric antigen receptor (CAR) T cells engineered to specifically target CD123, a protein expressed on AML cells, using a CAR construct comprising an anti-CD123 binding domain, a transmembrane domain, and an intracellular signaling domain, to enhance persistence and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cells are engineered to target AML cells, then tumor eradication capability is improved, but persistence of the infused CAR T cell product deteriorates
Solution Approach 1:
The patent modifies the CAR construct parameters by incorporating specific costimulatory domains (CD28 and 4-1BB) and optimizing the signaling configuration to enhance T cell persistence while maintaining tumor eradication capability. This parameter optimization resolves the contradiction between immediate efficacy and long-term persistence.
2Ease of manufacture
If standard therapy is used for AML, then treatment simplicity is maintained, but treatment effectiveness deteriorates
Solution Approach 1:
The CAR T cell therapy is engineered to autonomously recognize and eliminate AML cells through the CD123 target antigen without requiring external activation or complex administration protocols. The cells self-proliterate and persist in the patient's body, providing sustained therapeutic effect while maintaining relative simplicity in the treatment workflow.
Data Source
AI summary
The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.