Engineered Allogeneic Cells for Immune Evasion in Cell Therapy
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Solution Overview
Problem
Current clinical transplantation therapies, including cell therapies, face challenges due to the recipient's immune system rejecting allogeneic material, which reduces the efficacy of these treatments.
Innovation Solution
Engineered cells with modifications that increase expression of tolerogenic factors, reduce expression of CD142, and decrease expression of MHC class I and II molecules are developed to evade immune detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
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 treatment efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the expression levels of specific molecules on the cell surface. It increases expression of tolerogenic factors (CD47, HLA-G, PD-L1, IDO1, CTLA4-Ig) and decreases expression of immunogenic molecules (MHC class I and II, CD142). These parameter changes in molecular expression profiles enable the cells to evade immune detection while maintaining therapeutic function, thereby resolving the contradiction between therapy efficacy and immune rejection.
Solution Approach 2:
The patent uses tolerogenic factors as intermediary molecules that mediate between the allogeneic cells and the recipient's immune system. These factors (particularly CD47 binding to SIRPĪ±, HLA-G interactions, and PD-L1 binding to PD-1) act as protective intermediaries that prevent immune cell activation and attack, allowing the therapeutic cells to survive and function without causing strong immune rejection.
2Reliability
If the recipient's immune system detects allogeneic material, then immune rejection occurs, but this detection reduces the potential efficacy of transplantation therapies
Solution Approach 1:
The patent changes the immunological parameters of the cells by modulating surface molecule expression. Specifically, it upregulates tolerogenic markers (CD47, HLA-G, PD-L1) that signal 'self' or 'non-threatening' status to the immune system, while downregulating MHC class I/II and CD142 that are recognized as foreign. This parameter optimization allows cells to avoid immune detection while preserving their therapeutic productivity.
3Object-affected harmful factors
If expression of MHC class I and II molecules is reduced to evade immune detection, then immune recognition decreases, but this may affect cell function and survival
Solution Approach 1:
The patent introduces tolerogenic factors as intermediary protective molecules that compensate for reduced MHC expression. These factors (CD47, HLA-G, PD-L1, IDO1, CTLA4-Ig) act as alternative mediators that actively suppress immune cell activation and promote survival signals, thereby maintaining cell function and survival despite lower MHC class I/II expression levels that reduce immune recognition.
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 hyopimmunogenic cells. In some embodiments, the engineered cells comprise reduced expression of CD 142 and/or are administered in combination with an anti-coagulant.