Chimeric Receptor Engineering for Myeloid Cell Phenotype Control
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Solution Overview
Problem
Current approaches fail to effectively enhance myeloid cell activities such as activation, proliferation, survival, and functionality against cancer, as myeloid cells contribute to immunosuppressive environments that promote tumor growth and progression.
Innovation Solution
A chimeric receptor comprising an extracellular ligand-binding domain associated with cancer, a transmembrane domain, and a signaling domain is introduced into innate immune cells, activating signaling pathways that induce an M1 phenotype, pro-inflammatory cytokine secretion, and inhibition of immune checkpoint molecules, thereby enhancing myeloid cell activities against cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If myeloid cells are utilized for cancer therapy, then tumor antigen presentation and phagocytosis are enhanced, but immunosuppressive environment and tumor growth are promoted
Solution Approach 1:
The patent segments the myeloid cell population into different functional subsets (M1 macrophages with anti-tumor activity vs. M2 macrophages with pro-tumor activity) and uses chimeric receptors to selectively direct and enhance the anti-tumor subset while suppressing the pro-tumor subset, thereby resolving the contradiction between enhanced anti-tumor immunity and immunosuppression
Solution Approach 2:
The patent changes the functional parameters of myeloid cells by introducing chimeric receptors that alter cell activation states, cytokine production profiles, and phenotypic characteristics, transforming myeloid cells from immunosuppressive to immunostimulatory functions against cancer
2Reliability
If chimeric receptor is introduced to enhance myeloid cell activation, then anti-tumor functionality is improved, but cell complexity and manufacturing difficulty increase
Solution Approach 1:
The patent merges multiple functional domains into a single chimeric receptor molecule, combining the ligand-binding capability (to recognize tumor antigens) with the signaling domain (to activate anti-tumor responses), thereby simplifying the overall system architecture while achieving enhanced myeloid cell functionality
Solution Approach 2:
The chimeric receptor design incorporates universal signaling domains that can be paired with different ligand-binding specificities, allowing a single receptor framework to serve multiple anti-tumor functions across different cancer types, reducing the need for entirely separate complex systems
Data Source
AI summary
The present disclosure is related to compositions that include polynucleotides encoding chimeric receptors, methods of delivering polynucleotides encoding chimeric receptors to immune cells, and methods of using immune cells encoding chimeric receptors to treat or prevent cancer.