Post-Transplant Lymphoproliferative Disease (PTLD)
Post-transplant lymphoproliferative disease (PTLD) is one of the most common causes of cancer mortality among individuals with solid organ transplants. PTLD is classified as one of the most threatening forms of post-transplant malignancies. Our company offer fully integrated PTLD drug and therapy development services which makes us pioneers in PTLD drug development.
Introduction to PTLD
PTLD is a potential complication that may follow solid organ or hematopoietic stem cell transplant that has the potential of being fatal. It is characterized by uncontrolled proliferation of lymphoid tissue, often associated with Epstein-Barr Virus infection due to immunosuppressive therapy. The range of PTLD's incidence is between 1% and 20%, depending on the type of transplant, level of immunosuppression, and the recipient's EBV status before the transplant.
Pathogenesis of PTLD
The pathogenesis of PTLD lies primarily in EBV, which infects B-cells and results in immune evasion through latent infection. The post-transplant period of immune suppression permits uncontrolled proliferation of B-cells. Chronic inflammation further facilitates the condition by aiding in reactivation of the virus and infected cell expansion.
Fig.1 Pathogenetic mechanisms of early onset EBV-related PTLD. (Petrara, M.R., et al., 2011)Diagnostics Development of PTLD
Recent discoveries in PTLD diagnostics have concentrated on precise staged detection along with segregation of different disease forms. Methods like quantitative PCR are now implemented for measuring EBV DNA load in blood samples to EBV monitor and anticipate PTLD is effectively. Additional explored biomarkers like cell-free and circulating tumor DNA aim to provide extra diagnostic PTLD accuracy together with molecular insight into PTLD pathogenesis.
Therapy Development of PTLD
Small molecule drugs like mTOR inhibitors (Sirolimus) can decrease the risk of PTLD by modulating the immune response and inhibiting cell growth and are used in combination with chemotherapeutics like cyclophosphamide in the CHOP regimen to augment anti-tumor effects.
New therapies such as Donor Lymphocyte Infusions (DLI) and the new experimental CAR-T cell therapies are designed to improve the immune response toward tumor cells, particularly in PTLD, by employing the use of modified immune cells to recognize and destroy cancerous cells within the body.
The purpose of monoclonal antibodies such as rituximab is to target CD20 on B-cells during the therapeutic of B-cell PTLD. With the newer monoclonal antibody Obinutuzumab, there is hope for better therapeutic, as it binds to B-cells and helps them be eliminated more efficiently due to poor target binding.
The application of a gene therapy strategy includes the use of T-cells targeted against EBV infection to infected cells which may aid in immune restoration, or the use of gene delivery systems such as viral vectors to effect the death of the cancer cells or greatly enhance immune recognition.
Our Services
As a company we strive to be a partnership organization. We collaborate with clients in the creation of novel 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, 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 | |
We have acquired considerable knowledge and skill in the design and development, as well as, characterization of animal models that correlate well with the PTLD disease process and its therapy. The animal models are designed for safety and efficacy studies for the new therapies created.
Additionally, we provide more elaborate services for other models that modulate defined signaling networks or specific molecular targets.
If you are interested in any of our offerings, please contact us at your earliest convenience. We look forward to learning more about how we can create solutions that help you achieve your outcomes and goals.
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.