Selective IL2R/IL15R Inhibition for GvHD Treatment
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Solution Overview
Problem
Current treatments for graft versus host disease (GvHD), particularly acute and chronic forms, are limited and often compromise the therapeutic benefits of hematopoietic stem cell transplantation by either suppressing the immune system too much or not enough, leading to unmet medical needs in managing this condition.
Innovation Solution
Administering IL2 receptor (IL2R) or IL15 receptor (IL15R) inhibitors, alone or in combination with JAK inhibitors, to modulate immune responses and prevent or treat GvHD, thereby targeting specific signaling pathways without significantly disrupting the beneficial graft versus leukemia or tumor effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If strong immunosuppression is used to prevent or treat acute and/or chronic GvHD, then GvHD severity is reduced, but the beneficial GvL or GvT effect is abrogated
Solution Approach 1:
The patent segments the immune suppression approach by targeting specific cytokine receptors (IL-2R and IL-15R) rather than applying broad immunosuppression. This selective targeting allows suppression of GvHD while preserving other immune functions necessary for GvL effect.
Solution Approach 2:
The invention applies local quality by using antibodies that specifically bind to IL-2R or IL-15R on the surface of donor T cells, creating a localized effect at the receptor level. This specificity enables differentiation between suppressing harmful GvHD pathways and maintaining beneficial GvL activity.
2Reliability
If weak or no immunosuppression is used, then the beneficial GvL or GvT effect is preserved, but the risk or severity of acute and/or chronic GvHD increases
Solution Approach 1:
The patent introduces intermediary substances (anti-IL-2R or anti-IL-15R antibodies) that mediate between the donor T cells and the host tissues. These antibodies act as intermediaries that selectively block harmful cytokine signaling while allowing other immune interactions to proceed, thus reducing GvHD risk without compromising GvL effect.
3Object-affected harmful factors
If conventional GvHD treatments are used, then GvHD symptoms are managed, but the therapeutic effectiveness of alloHSCT is compromised
Solution Approach 1:
The invention changes the parameter of immune suppression from non-specific to specific by targeting IL-2R and IL-15R signaling pathways. This parameter change allows for more precise control of GvHD management while preserving the therapeutic effectiveness of the underlying alloHSCT by avoiding broad immunosuppression.
Data Source
AI summary
Provided herein, in certain aspects, are methods of preventing or treating acute graft versus host disease comprising administration of an IL2 receptor inhibitor, an IL15 receptor inhibitor, or an IL2/IL15 receptor inhibitor, each in combination with administration of a JAK inhibitor. Also provided herein, are methods of preventing or treating chronic graft versus host disease comprising administration of an IL2 receptor inhibitor, an IL15 receptor inhibitor, or an IL2/IL15 receptor inhibitor, each as a monotherapy.