Acute Graft Versus Host Disease (Acute GVHD)
Acute Graft Versus Host Disease (Acute GVHD) is one of the severe complications that arise from allogeneic stem cell transplantation, in which the immune cells of the donor attack the recipient's body. There is some evidence that pathophysiological-based prevention and treatment measures of Acute GVHD have the potential of reducing the incidence of these pathologies substantially. Our Company is leading the efforts of the branch, offering comprehensive development services for drugs and therapeutics for treatment of Acute GVHD.
Introduction of Acute GVHD
Acute GVHD is a frequent complication of the Allogeneic hematopoietic stem cell transplantation procedure, and it is associated with a relatively high rate of morbidity and organ system failure. The range of stem cell transplant patients who experience this condition is between 30 to 50 percent. It ranges from rashes, nausea, vomiting, diarrhea, abdominal cramps, hyperbilirubinemia and jaundice from bile duct and cholestatic damage, and predominantly involves sclera, skin, liver, and intestines.
Pathophysiology of Acute GVHD
Acute GVHD develops in a stepwise fashion: first, there is the initiation which is accompanied with tissue damage as a result of the pre-transplant interventions with the aim of destruction of the malignancy, which starts the activity of the bodys' antigen presenting cells; then, there is CD4 with cytotoxic CD8 T cells activation of donor T cells to host APCs; last, there is the effector phase with T-cells and cytokines attacking the epithelial cells on the organs, inducing apoptosis and other signs of severe Acute GVHD.
Fig.1 Pathophysiology of Acute GVHD. (Malard, F., Holler, E., et al., 2023)Diagnostics Development of Acute GVHD
The diagnosis procedure for Acute GVHD includes assessment, histological study, and increasing use of biomarker evaluation. The primary aim is to determine the precise nature of the disease if present and its severity in order to make appropriate treatment choices.
The assessment is targeted, that is, the patients are screened for the common features of Acute GVHD and, depending on the Organ(s) involved and the Inflammation level, Disease Staging is done. Histological examination by means of biopsy allows observation of the pathologic processes on the tissues that have been destroyed, diagnosing Acute GVHD from other ailments with its particular patterns of cellular damage and infiltration. A variety of sTNFR1, Reg3α, ST2, and Elafin were discovered as a result of biomarker innovation.
Therapeutics Development of Acute GVHD
- Types of Acute GVHD Therapy Development
With agents like Ruxolitinib and Itacitinib, immune activity is decreased by targeting the JAK pathways, and antibodies against TNF-α and CD52 provide additional ways for inflammation and immune response to be controlled.
Including Mesenchymal Stromal Cells (MSCs), Regulatory T Cells (Tregs), Natural Killer (NK) Cells, and Chimeric Antigen Receptor T Cells (CAR-T cells), are highly promising in the management of Acute GVHD.
- Challenges of Acute GVHD Therapy Development
Targeting Acute GVHD is challenging due to the complex nature of the disease's immune components which are not yet well understood.
Although individual tailoring of therapeutics based on risk factors and disease profile is necessary, it poses specific challenges.
Chronic GVHD continues to pose long-term complications that, along with insufficient or no positive response from treatment, calls for novel drugs and better strategies for dealing with the disease.
Our Services
We are also one of the leaders in developing services for drug and therapy for Acute GVHD. Using our knowledge in biomarker discovery, diagnostics creation, and targeted therapy design, we aim to improve and stimulate the development of Acute GVHD therapies in the international pharmaceutical market.
Therapy Development Platforms
Animal Models of Acute GVHD
A major focus of preclinical work on gastric cancer therapy revolves around the need to develop animal models. We have developed relevant animal models which have accurate characterization of the disease and response to therapy. This allows for assessing the safety and efficacy of the 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, 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 | ||
Along with these models, our innovative services cover other models affecting certain signaling pathways and T cell activation, proliferation pathways, and molecular targets too.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
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.