Post-Transplant Lymphoproliferative Disease (PTLD)
Post-transplant lymphoproliferative disease (PTLD) represents a serious complication in solid organ transplantation and is the first cause of cancer-related mortality in this population. Specialized drug and therapy development services are essential to enhance PTLD research. Our company takes the lead in providing comprehensive PTLD drug and therapy development solutions.
Introduction to PTLD
PTLD is a potentially life-threatening complication that can occur after solid organ or hematopoietic stem cell transplantation. It involves the uncontrolled proliferation of lymphoid cells, often driven by Epstein-Barr Virus (EBV) infection due to immunosuppressive therapy. The incidence of PTLD varies widely, ranging from 1% to 20%, depending on the type of transplant, the intensity of immunosuppression, and the recipient's EBV status prior to transplantation.
Pathogenesis of PTLD
The pathogenesis of PTLD largely revolves around the EBV, which infects B-cells and disrupts immune surveillance by maintaining a latent infection. This compromised immune function post-transplant allows for uncontrolled B-cell proliferation. Chronic inflammation further exacerbates this condition, aiding the reactivation of the virus and promoting the expansion of infected cells.
Fig.1 Pathogenetic mechanisms of early onset EBV-related PTLD. (Petrara, M.R., et al., 2011)Diagnostics Development of PTLD
The recent advancements in diagnostics for PTLD focus on early detection and accurate differentiation of the disease stages. Molecular techniques such as quantitative PCR are now routinely used to measure EBV DNA load in blood samples, providing a way to monitor viral activity and predict PTLD risk effectively. New biomarkers, including cell-free DNA and circulating tumour DNA, are being explored to enhance diagnostic precision and offer insights into the molecular underpinnings of PTLD.
Therapy Development of PTLD
Small molecule inhibitors such as mTOR inhibitors (e.g., Sirolimus) help reduce PTLD risk by suppressing immune responses and inhibiting cellular proliferation, often used alongside chemotherapeutics like cyclophosphamide in regimens such as CHOP to enhance antitumor effects.
Innovative cell-based therapies like Donor Lymphocyte Infusions (DLI) and experimental CAR-T cell therapies aim to enhance the body's immune response against tumor cells, specifically targeting malignancies in PTLD using genetically engineered cells.
Monoclonal antibodies such as Rituximab target CD20 on B-cells to induce remission in B-cell PTLD, with newer antibodies like Obinutuzumab offering potentially improved efficacy through better target binding and B-cell depletion.
Gene therapy strategies involve using EBV-specific T-cell therapy to target viral infected cells and potentially restore immune control, or employing viral vectors to deliver therapeutic genes that induce cancer cell death or boost immune recognition.
Our Services
At our company, we prioritize a partnership-driven approach. We work together with our clients to develop innovative PTLD therapies.
Platforms of PTLD Therapy Development
Animal Models of PTLD
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.
| Non-Genetically Engineering Models | ||
| Our company specializes in delivering top-notch services to create NON-GEMs. We provide diverse model choices customized to meet specific research needs related to PTLD. | ||
| Optional Models |
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| 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 PTLD. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services resonate with you, we invite you to contact us whenever works best for you. Let's discuss customizing our solutions to align seamlessly with your objectives and aspirations.
References
- Petrara, M.R., et al., "Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment." Cancer Lett, (2015). 369(1): p. 37-44.
- Stojanova, J., et al., "Post-transplant lymphoproliferative disease (PTLD): Pharmacological, virological and other determinants." Pharmacol Res, (2011). 63(1): p. 1-7.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.