Hypoimmunogenic Cell Engineering via RFX Pathway Suppression
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Solution Overview
Problem
Existing cell therapy approaches face challenges such as chemical and molecular interference, cell-to-cell interference, competition for nutrients, cellular exhaustion, and manufacturing issues, leading to a dearth in cell therapy approvals for targeting complex diseases like neoplasia and tumors.
Innovation Solution
Genetic modification of regulatory factor X (RFX) and other genes in immunogenic human cells to reduce protein expression, forming hypoimmunogenic cells through embryoid bodies, and subjecting them to an immune system to alter immunogenicity, thereby reducing immune responses and alloreactive T cell cytotoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell therapy approaches are used to target complex diseases, then therapeutic efficacy is improved, but immune rejection and cellular exhaustion occur
Solution Approach 1:
The patent applies this principle by genetically modifying allogeneic cells to reduce or eliminate MHC class I and class II molecules, thereby converting the harmful immune recognition into a beneficial hypoimmunogenic state. The modified cells retain therapeutic function while becoming invisible to the host immune system, allowing sustained efficacy without rejection
Solution Approach 2:
The patent changes the immunogenic parameters of therapeutic cells by knocking out or downregulating specific genes (MHC class I, MHC class II, RFX5, RFXANK, RFXAP, CD58, B2M, CIITA). This parameter modification creates hypoimmunogenic cells that can persist in the host without triggering immune rejection, thereby improving therapeutic reliability
2Object-affected harmful factors
If genetic modification is applied to reduce immunogenicity, then immune response is reduced, but manufacturing complexity increases
Solution Approach 1:
The patent segments the complex immunogenicity reduction task into multiple manageable genetic modifications. Instead of attempting to eliminate all immune recognition at once, the invention systematically knocks out or downregulates specific genes (MHC class I, MHC class II, RFX5, RFXANK, RFXAP, CD58, B2M, CIITA) in a stepwise manner, making the manufacturing process more controllable and less complex
Solution Approach 2:
The patent uses standardized genetic modification techniques to change immunogenic parameters systematically. By establishing a set of predefined genetic knockouts that consistently produce hypoimmunogenic cells, the manufacturing process becomes more predictable and scalable, reducing overall complexity despite the multiple modifications required
Data Source
AI summary
Provided herein are methods of hypoimmunogenicity, such as bioengineering methodologies and materials, including hypoimmunogenicity (such as engineering hypoimmunogenicity) methodologies and materials useful in, for example, genetically modifying and/or otherwise altering at least one target gene or gene product, processes for producing hypoimmunogenic cells (such as engineered hypoimmunogenic cells), manufacturing of hypoimmunogenic cellular compositions (such as engineered hypoimmunogenic cellular compositions), hypoimmunogenic cell systems (such as engineered hypoimmunogenic cell systems) and uses thereof.