IL-33 Activated ILC2 Cells for GvHD Treatment
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Solution Overview
Problem
Current treatments for graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS) following allogeneic stem cell or bone marrow transplants are limited, with corticosteroid therapies causing significant side effects and poor patient outcomes, and there is a need for effective prevention and treatment methods.
Innovation Solution
The use of IL-33 activated type 2 innate immune cells (ILC2) as a therapeutic approach, characterized by specific markers and cytokine profiles, which are administered to patients to modulate the cytokine environment from Th1/Th17 to Th2, reducing the severity of GvHD and IPS, and potentially administered as a co-infusion with transplants to prevent these conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If corticosteroid therapy is used to treat graft versus host disease, then the disease symptoms are suppressed, but significant side effects occur including infectious complications, bone disturbances and metabolic changes
Solution Approach 1:
The patent uses regulatory T cells (Tregs) as intermediary cells to mediate the immunosuppressive effect. Instead of directly administering corticosteroids that cause widespread side effects, Tregs are administered to selectively suppress the harmful immune response in GvHD while preserving normal immune function, thus treating the disease without the broad harmful effects of corticosteroids
Solution Approach 2:
The patent changes the therapeutic parameter from chemical immunosuppression (corticosteroids) to cellular immunosuppression (Tregs). This parameter change allows for more selective and controlled immunosuppression, achieving disease suppression while minimizing the harmful side effects associated with systemic corticosteroid therapy
2Object-generated harmful factors
If corticosteroid therapy is used for GvHD treatment, then acute symptoms are managed, but patient survival outcome remains dismal with only 10% surviving one year
Solution Approach 1:
The patent employs Tregs in preliminary action to prevent the development of severe GvHD in the first place. By administering Tregs prophylactically or at the onset of GvHD, the disease progression is blocked before it reaches the steroid-refractory stage, thereby improving long-term survival outcomes rather than merely managing acute symptoms
3Reliability
If allogeneic stem cell transplant is performed to treat high-risk leukemia and malignancies, then curative potential is achieved, but graft versus host disease remains a major obstacle
Solution Approach 1:
The patent applies preliminary anti-action by administering Tregs before or at the time of allogeneic stem cell transplant to preemptively counteract the development of GvHD. This preliminary protective measure allows the transplant to proceed with curative intent while having the harmful GvHD response blocked in advance, thus enabling curative treatment without the major obstacle of GvHD
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The administration of IL-33 activated ILC2 cells significantly reduces the risk and severity of GvHD and IPS, improves patient survival, and can be used to shift the cytokine micro-environment, thereby ameliorating symptoms and preventing the onset of these conditions.
Implementation Method 1
The use of IL-33 activated type 2 innate immune cells (ILC2) as a therapeutic approach, characterized by specific markers and cytokine profiles, which are administered to patients to modulate the cytokine environment from Th1/Th17 to Th2
Data Source
AI summary
ILC2 cells play a role in the pathogenesis of graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS), both conditions associated with allogeneic stem cell transplantation. Infusion of IL-33 activated ILC2 cells into patients with ongoing GvHD or IPS, or prior to onset of GvHD or IPS in susceptible patients, substantially ameliorates the disease and improves survival.