Engineered Myeloid Cells for Graft Tolerance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies fail to effectively induce immunosuppression and tolerance, leading to rejection of transplanted tissues and organs, as well as autoimmune diseases, due to the immune system's inability to distinguish between self and non-self antigens.
Innovation Solution
Engineering myeloid cells or progenitor cells to increase the expression of cellular FLICE [Fas-associated death domain (FADD)-like IL-1β-converting enzyme]-inhibitory protein (CFLAR), which enhances their immunosuppressive activity, thereby reducing immune responses and promoting tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the immune system responds to foreign antigens, then protection against pathogens is improved, but rejection of transplanted tissues and organs occurs
Solution Approach 1:
The patent uses engineered myeloid cells expressing CFLAR as intermediary agents that mediate between the immune system and transplanted tissues. These cells suppress alloreactive T cell responses through CFLAR-mediated inhibition of apoptosis, thereby preventing graft rejection while maintaining immune surveillance against pathogens
Solution Approach 2:
The patent changes the cellular parameter of CFLAR expression levels in myeloid cells. By overexpressing CFLAR in engineered myeloid cells, the patent modifies the apoptotic sensitivity of these cells, enabling them to suppress T cell responses and prevent graft rejection without compromising overall immune function
2Reliability
If the immune system activates against antigens, then immune response effectiveness is improved, but autoimmune disorders occur due to loss of tolerance against self-antigens
Solution Approach 1:
The patent employs engineered myeloid cells as intermediary regulators that restore tolerance to self-antigens. These cells express CFLAR to suppress autoreactive T cell responses through inhibition of apoptosis, thereby preventing autoimmune disorders while preserving the immune system's ability to respond effectively to foreign pathogens
Solution Approach 2:
The patent applies preliminary anti-action by pre-engineering myeloid cells with high CFLAR expression before their interaction with the immune system. This preemptive modification enables these cells to actively suppress autoreactive T cell responses and establish tolerance to self-antigens before autoimmune pathology develops
Data Source
Figure 1A~1B
Figure 2A~2B
Figure 3
AI summary
The present invention relates to cells which are engineered so as to increase the cellular level of cellular FLICE [Fas-associated death domain (FADD)-like IL- 1 β-con verting enzyme] - inhibitory protein (CFLAR). The engineered cells have the ability to induce tolerance. Enhanced tolerogenicity is useful for prolonging survival of a foreign transplant and for treatment of autoimmune diseases.