Immune Checkpoint Engager Cells to Mitigate Allogeneic Rejection
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Solution Overview
Problem
Existing immune cell therapies face challenges in effectively modulating immune responses to prevent rejection and enhance therapeutic efficacy, particularly in the context of allogeneic stem cell therapies, which can trigger immune rejection due to mismatched histocompatibility and immune recognition.
Innovation Solution
Development of Immune Checkpoint Engager (ICE) cells with enhanced immune checkpoint engagement functions, such as PD-1 engager cells, hypoimmune pluripotent cells, and reduced HLA expression, to protect cells from immune killing and facilitate transplantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If allogeneic stem cell therapies are used to treat diseases, then therapeutic efficacy is improved through cell transplantation, but immune rejection occurs due to mismatched histocompatibility and immune recognition
Solution Approach 1:
The patent introduces immune checkpoint engager cells as intermediary cells that express PD-1 and other immune checkpoint molecules to mediate between the transplanted stem cells and the host immune system. These ICE cells act as a protective interface that engages inhibitory immune receptors to suppress rejection responses while allowing therapeutic cells to function
Solution Approach 2:
The patent modifies the immunogenicity parameters of transplanted cells by reducing HLA expression and engineering hypoimmune phenotypes. This involves changing the expression levels of histocompatibility molecules and immune recognition markers to create cells that are less visible to the immune system while maintaining therapeutic function
2Object-affected harmful factors
If immune checkpoint molecules are engaged to protect transplanted cells, then immune rejection is reduced, but the complexity of cell engineering increases
Solution Approach 1:
The patent creates universal immune checkpoint engager cells that can protect multiple different types of transplanted stem cells across various therapeutic applications. The ICE cell platform with standardized PD-1 and other checkpoint molecule expression can be applied to mesenchymal stem cells, induced pluripotent stem cells, and other cell types without redesigning the immune protection mechanism for each cell type
Solution Approach 2:
The patent performs preliminary engineering of immune checkpoint molecules and hypoimmune phenotypes during cell manufacturing before transplantation. By pre-engineering the ICE cells with PD-1 expression and reduced HLA levels prior to implantation, the complex immunoprotection measures are established in advance rather than requiring complex in vivo interventions after transplantation
Data Source
AI summary
The invention provides cells that have an increased immune checkpoint engagement function (Immune Checkpoint Engager “ICE” cells). The ICE cells comprise an engager molecule' expressed on a cell surface, wherein said engager molecule engages with an immune checkpoint molecule on an immune cell, wherein said engager molecule is expressed at least at a level that protects said ICE cell from being killed by said immune cell.