Graft-Versus-Host Disease (GVHD)

Graft-Versus-Host Disease (GVHD) is a major, often life-threatening, complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). MyD88 targeted therapy being developed by Protheragen aims to modify the host immune response system which plays an important role in the GVHD aggravation.

Introduction to Graft-Versus-Host Disease

GVHD remains a huge barrier to achieving success with HSCT surgeries that are performed to treat advanced blood cancer and other illnesses. It can be acute (till the 100th day post surgery) or chronic (afterwards – tends to be more severe). The different forms of inflammation caused by transplantation differ depending on HLA compatibility, intensity of the conditioning pre-transplant treatment regimen, and numerous other donor/recipient factors). It is clear now that the major inflammation perpetrator towards GVHD (and its exacerbations) is the innate immune system that slowly becomes activated in the host and is mostly known for its MyD88 system.

Pathogenesis of Graft-Versus-Host Disease

GVHD develops when donor-derived immune effector cells recognize host tissues as foreign, triggering inflammation. Activated donor T cells release pro-inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-1) and recruit cytotoxic effectors that attack the skin, liver, gastrointestinal tract, and other organs. Host antigen-presenting cells, via MyD88-dependent signaling, and dysregulated innate immunity amplify inflammation, ultimately driving tissue fibrosis and multi-organ failure.

Fig.1 Schema of possible mechanisms of action of MyD88−/− donor T cells during aGVHD. (Griesenauer et al., 2019)

MyD88-Targeted Therapeutic Development for Graft-Versus-Host Disease

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen provides MyD88-targeted therapeutic discovery and advanced disease models development services specifically tailored for Graft-Versus-Host Disease. Our disease models enable preclinical intervention development aimed at mitigating host innate immune activation and subsequent tissue damage in GVHD.

Therapeutic Discovery Platform for Graft-Versus-Host Disease

• Small Molecule Inhibitors
• Monoclonal Antibodies

• siRNA Development
• Mimetic Peptides

Disease Models Development for Graft-Versus-Host Disease

Protheragen offers extensive in vitro & in vivo models for GVHD, including cell-based models, organoid models, and animal models, enabling the comprehensive evaluation of MyD88-targeted therapeutic strategies. These models recapitulate key aspects of GVHD pathogenesis, providing critical insights into therapeutic efficacy against the complex pathophysiology of GVHD.

• Recipient APC-Donor T Cell Co-culture Systems
• Host Epithelial/Endothelial Cell Culture Models
• Gut Organoid Models

• Major MHC-Mismatched Allo-HSCT Mouse Models
• Conditioning Regimen-Induced Tissue Injury Models
• Microbiota Dysbiosis Models in Allo-HSCT Setting

Protheragen advances MyD88-targeted drug discovery for GVHD through end-to-end solutions. We provide comprehensive proposal tools encompassing disease model development, pharmacokinetics and drug safety evaluation, alongside support for investigator-initiated trials.

If you are interested in our services, please don't hesitate to contact us.

References

• Griesenauer, B., et al. "St2/Myd88 Deficiency Protects Mice against Acute Graft-Versus-Host Disease and Spares Regulatory T Cells." J Immunol 202.10 (2019): 3053-64.
• Xing, S., et al. "Host Myd88 Signaling Protects against Acute Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation." Clin Exp Immunol 195.1 (2019): 121-31.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.