Grégoire, S. (Simon) (2018) Rituximab and brentuximab vedotin is synergistic in lymphoblastoid cell lines. thesis, Medicine.
Full text available on request.Abstract
In order to prevent organ damage and other chemotherapy related morbidity and mortality in patients with an Epstein-Barr Virus (EBV) positive Post Transplant Lymphoproliferative Disorder (PTLD), it is desirable to avoid the use of chemotherapy. We performed this study to find new rational drug combinations that could abrogate chemotherapy for this group of patients. Therefore, we looked into CD30 as a potential target, as it is expressed on EBV positive PTLDs and is a target for the drug brentuximab vedotin. We selected Lymphoblastoid Cell Lines (LCLs) as an in vitro model for EBV positive PTLDs and used these to study the effect of rituximab (which is currently used in the treatment of PTLDs) and brentuximab vedotin as single agents and in combination. Cell viability assays showed that 10μg/ml cross-linked rituximab killed 68-87% of cells after 24 hours, and 30 μg/ml brentuximab vedotin killed 26-54% of cells after 72 hours. Our study found that the combination treatment with these drugs was synergistic, killing 75-92% of cells after 72 hours. At clinically relevant and tolerable concentrations, the combination of rituximab and brentuximab vedotin was effective in killing EBV infected CD20 and CD30 positive B-cells. As this immune phenotype is present in >85% of PTLD cases, we expect this treatment to be effective in the majority of PTLD patients. This study provides the theoretical basis for practical implementation of this new treatment option in the group of EBV positive PTLD patients. It could greatly decrease treatment time, improve disease outcome and increase overall survival. But most importantly, it promises to be an effective chemotherapy-free treatment option for PTLD patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | PIs: and Visser, dr. L. and Meerten, dr. T. van and Dept: Hematology & Pathology and UMCG / UG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:49 |
| Last Modified: | 25 Jun 2020 10:49 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/977 |
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