Chimeric Receptor Design for CLL-1 Targeting
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Solution Overview
Problem
Current therapies for treating CLL-1 related diseases and disorders, such as acute myeloid leukemia and autoimmune diseases, have varying levels of effectiveness with undesired side effects, necessitating the development of novel and improved therapeutic approaches.
Innovation Solution
Engineered immune cells, specifically chimeric antigen receptors (CARs) and T cell receptors (TCRs), are designed with CLL-1 specific antigen binding molecules, including novel CD28 extracellular sequences, to enhance antigen recognition and immune cell activation, incorporating specific antigen binding molecules, costimulatory domains, and activating domains for improved therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat CLL-1 related diseases, then treatment can be provided, but effectiveness varies and undesired side effects occur
Solution Approach 1:
The chimeric antigen receptor is divided into distinct functional domains: an antigen-binding module (single-chain variable fragment) that specifically recognizes CLL-1, and a signaling module (CD3 zeta chain) that triggers immune cell activation. This segmentation allows for specific targeting of CLL-1 expressing cells while minimizing off-target effects and reducing undesired side effects associated with non-specific immunosuppressive therapies.
2Reliability
If engineered immune cells with CLL-1 specific antigen binding molecules are designed, then antigen recognition and immune cell activation are enhanced, but device complexity increases
Solution Approach 1:
The invention merges the antigen-binding function of a single-chain variable fragment (scFv) with the signaling function of the CD3 zeta chain into a single chimeric antigen receptor molecule. This unified structure integrates extracellular antigen recognition domains with intracellular signaling domains, enabling both specific CLL-1 binding and robust immune cell activation through one integrated receptor complex on the immune cell surface.
Solution Approach 2:
The chimeric antigen receptor design incorporates multiple functional capabilities within a single molecular construct: (1) specific antigen binding through the scFv portion, (2) signal transduction through the CD3 zeta chain, and (3) immune cell activation leading to cytolytic activity and cytokine production. This multi-functionality enhances therapeutic effectiveness while the modular design allows for potential standardization and scalability.
Data Source
AI summary
Antigen binding molecules, chimeric receptors, and engineered immune cells are disclosed in accordance with the invention. The invention further relates to vectors, compositions, and methods of treatment and/or detection using the antigen binding molecules and engineered immune cells.