Acute Graft Versus Host Disease (Acute GVHD)
Acute Graft Versus Host Disease (Acute GVHD) is a significant complication following allogeneic stem cell transplantation, where donor immune cells attack the recipient's body. Experimental prevention and therapy based on the pathophysiology of Acute GVHD hold promise for significantly reducing the incidence of this condition. Our Company stands at the vanguard of offering all-encompassing services for developing drugs and therapeutics targeting Acute GVHD.
Introduction of Acute GVHD
Acute GVHD is a common complication triggered by allogeneic hematopoietic stem cell transplantation, leading to immune dysfunction and tissue or organ malfunction. The occurrence rate among transplant recipients is between 30% and 50%. It typically affects the skin, liver, and gastrointestinal tract of individuals, manifesting as skin rashes, nausea, vomiting, diarrhea, crampy abdominal pain, and hyperbilirubinemia with jaundice due to bile duct damage and cholestasis.
Pathophysiology of Acute GVHD
The progression of Acute GVHD occurs in three stages: initiation, where pre-transplant therapy damages tissues, activating APCs; T-cell activation, where donor T cells recognize host antigens on APCs, triggering Acute GVHD with CD4 and CD8 involvement; and the effector stage, where T cells and cytokines attack organ epithelial cells, causing apoptosis and typical Acute GVHD symptoms.
Fig.1 Pathophysiology of Acute GVHD. (Malard, F., Holler, E., et al., 2023)Diagnostics Development of Acute GVHD
The diagnostics for Acute GVHD involve a combination of assessment, histological examination, and, increasingly, biomarker analysis. The goal is to accurately identify the presence and severity of the condition to guide therapy decisions.
Assessment primarily involves evaluating individuals for common symptoms of Acute GVHD and staging the disease based on the extent of organ damage and the level of inflammation. Histological examination uses biopsy methods to observe the pathological conditions of damaged tissues, differentiating Acute GVHD from other diseases based on its unique cellular damage and infiltration patterns. Advances in biomarker research have identified markers like sTNFR1, Reg3α, ST2, and Elafin.
Therapeutics Development of Acute GVHD
- Types of Acute GVHD Therapy Development
Agents like Ruxolitinib and Itacitinib target JAK pathways to reduce immune system activity, while antibodies against TNF-α and CD52 offer alternative mechanisms to control inflammation and immune response.
Including Mesenchymal Stromal Cells (MSCs), Regulatory T Cells (Tregs), Natural Killer (NK) cells, and Chimeric Antigen Receptor T Cells (CAR-T cells), showing significant potential in treating Acute GVHD.
- Challenges of Acute GVHD Therapy Development
Understanding the intricate immune mechanisms driving Acute GVHD is crucial but challenging due to its complex nature.
Tailoring therapeutics to individuals based on their specific risk factors and disease characteristics is essential but remains a significant challenge.
Despite advancements, many individuals fail to respond adequately to current therapeutics, and long-term complications like chronic GVHD persist, indicating a need for more effective therapeutics and comprehensive management strategies.
Our Services
At our company, we are at the forefront of Acute GVHD drug and therapy development services. Through our expertise in biomarker identification, diagnostics development, and targeted therapy development, we strive to advance the field and accelerate the development of Acute GVHD therapies for the global pharmaceutical industry.
Therapy Development Platforms
Animal Models of Acute GVHD
Animal models play a crucial role in preclinical research for gastric cancer therapy. We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Induced Animal Models | |||
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| Our company specializes in developing induced animal models that faithfully replicate the pathology and immunological features of Acute GVHD. One widely used induced animal model in Acute GVHD research is the CD3 Antibody-Induced Model. In this model, Acute GVHD is induced in recipient animals, resulting in T cell activation and subsequent tissue damage similar to that seen in human Acute GVHD. | |||
| Optional Models | CD3 Antibody-Induced Model | ||
| Genetically Engineered Models | |||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Acute GVHD. | |||
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| Optional Species | Mice, Rats, Others | ||
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways, T cell activation and proliferation pathways, and molecular targets.
Regardless of the stage of your research, we are prepared to support your endeavors with our research services. We invite you to contact us to learn more about our services and to discuss service quotes.
References
- Malard, F., et al., "Acute graft-versus-host disease." Nat Rev Dis Primers (2023). 9(1): p. 27.
- Zeiser, R. and Blazar, B.R., "Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy." N Engl J Med (2017). 377(22): p. 2167-2179
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.