Allogeneic Cell Therapy Evasion of Immune Rejection
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Solution Overview
Problem
Clinical transplantation therapies, including cell therapies, face challenges due to the recipient's immune system rejecting allogeneic material, leading to reduced efficacy and potential adverse effects, necessitating improved allogenic cells that evade immune detection.
Innovation Solution
Engineered cells with modifications that increase expression of tolerogenic factors, such as CD46, CD59, and specific MHC molecule reductions, are developed to reduce immune recognition, utilizing genetic modifications and gene editing techniques like CRISPR-Cas to enhance CD47 expression and inhibit MHC class I and II molecule expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If allogeneic cells are used for transplantation therapy, then the potential efficacy and positive effects of transplantation therapies are enhanced, but the recipient's immune system rejects the allogeneic material, reducing efficacy and causing adverse effects
Solution Approach 1:
The patent applies parameter changes by modifying the expression levels of specific surface molecules on allogeneic cells. It increases the expression of tolerogenic factors (CD47, HLA-E, HLA-G, PD-L1) and complement regulatory proteins (CD46, CD55, CD59) while decreasing the expression of immunogenic molecules (MHC class I and II). These parameter changes in molecular expression profiles enable the cells to evade immune detection and rejection, thereby maintaining therapeutic efficacy without causing immune-mediated adverse effects
Solution Approach 2:
The patent employs a composite approach by combining multiple genetic modifications in a single cell type. The engineered cells simultaneously express multiple tolerogenic factors and complement regulatory proteins while lacking classical MHC molecules. This composite modification strategy creates cells with enhanced immunoevasive properties that overcome the limitations of single-modification approaches, allowing successful allogeneic transplantation without immune rejection
2Reliability
If the recipient's immune system detects allogeneic cells, then immune rejection occurs, but this detection reduces the potential efficacy of transplantation therapies
Solution Approach 1:
The patent applies the extraction principle by removing or reducing the expression of classical MHC class I and class II molecules from the allogeneic cell surface. These MHC molecules are the primary targets for immune system detection through T-cell recognition. By taking out these immunogenic elements while retaining essential cell functions, the engineered cells become difficult for the recipient's immune system to detect, thereby preventing rejection and maintaining therapeutic efficacy
3Object-affected harmful factors
If tolerogenic factors and complement regulatory proteins are increased, then immune recognition is reduced, but this requires genetic modifications and gene editing techniques
Solution Approach 1:
The patent applies preliminary action by performing genetic modifications ex vivo before cell transplantation. The allogeneic cells are engineered outside the patient's body to overexpress tolerogenic factors and complement regulatory proteins, and to reduce MHC expression, prior to being transplanted into the recipient. This preliminary genetic engineering ensures that the cells are pre-equipped with immunoevasive properties, eliminating the need for complex immunosuppressive protocols after transplantation and simplifying the overall treatment approach
Data Source
AI summary
Provided are engineered cells containing one or more modifications, such as genetic modifications, for use in allogeneic cell therapy. In some embodiments, the engineered cells are hypoimmunogenic cells. In some embodiments, the engineered cells comprise increased expression of CD46 and CD59.