Hypoimmunogenic Cell Therapy for Repeated Dosing
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Solution Overview
Problem
Regenerative cell therapy faces challenges due to immune rejection of allogeneic materials, limiting the efficacy of tissue regeneration therapies.
Innovation Solution
Administration of hypoimmunogenic cells with reduced expression of MHC class I and II human leukocyte antigens and exogenous CD47 polypeptides, potentially combined with chimeric antigen receptors, to evade immune detection and promote therapeutic effects without immunosuppressive agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If allogeneic cells are administered for regenerative therapy, then tissue regeneration is achieved, but immune rejection occurs reducing therapeutic efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the immunogenicity parameters of the cells through genetic engineering. Specifically, MHC class I and II expression is reduced while CD47 is overexpressed, fundamentally changing the cells' interaction with the immune system. This allows allogeneic cells to evade immune detection and rejection, maintaining therapeutic efficacy across multiple administrations without requiring immunosuppression.
Solution Approach 2:
The patent creates composite cellular structures by combining multiple genetic modifications within single cells. The cells simultaneously exhibit reduced MHC class I, reduced MHC class II, and overexpressed CD47, creating a composite immunophenotype that provides synergistic protection against both humoral and cellular immune responses, enabling repeated administrations.
2Productivity
If repeated administrations of cells are performed to enhance therapeutic effect, then regenerative potential increases, but immune system detects and rejects the cells
Solution Approach 1:
The patent applies preliminary action by pre-modifying the cells with reduced MHC and overexpressed CD47 before administration. This preliminary genetic engineering ensures the cells are pre-equipped with immune-evasive properties, allowing them to survive and function upon repeated administrations without being detected or rejected by the recipient's immune system.
Solution Approach 2:
The patent enables periodic action by designing cells that can be administered in multiple doses at intervals. The modified cells maintain their immunoevasive characteristics throughout the treatment regimen, allowing for periodic re-administration to sustain or enhance therapeutic effects without accumulating immune rejection.
3Reliability
If immunosuppressive agents are used to prevent rejection, then cell survival improves, but side effects and reduced overall therapy effectiveness occur
Solution Approach 1:
The patent converts the harmful immune system into a non-responsive state by modifying cell surface markers. Instead of suppressing the immune system systemically with drugs, the modified cells essentially make the immune system 'blind' to them through reduced MHC expression and increased CD47, converting potential harm into benign coexistence without immunosuppressive side effects.
Data Source
AI summary
Disclosed herein are methods of treating a disorder in a patient by administering immune evading cells. In some embodiments, the patient receives more than one administration of such cells. In some embodiments, the cells disclosed herein have reduced levels or activities of MHC I and/or MHC II human leukocyte antigens. In some embodiments, the cells are derived from primary T cells or pluripotent stem cells that evade immune recognition. In some embodiments, the cells comprise a chimeric antigen receptor.