Development of Novel Patient-derived Xenograft Model of Chronic Lymphocytic Leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F20%3A00073419" target="_blank" >RIV/65269705:_____/20:00073419 - isvavai.cz</a>

Result on the web

<a href="https://www.ceitec.eu/abstract-book-final-docx-pdf/f36324" target="_blank" >https://www.ceitec.eu/abstract-book-final-docx-pdf/f36324</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Development of Novel Patient-derived Xenograft Model of Chronic Lymphocytic Leukemia

Original language description

Patient-derived xenografts (PDX) enable therapy testing and study of cancer evolution on a genetic background of individual patients. We aim to develop a novel murine PDX model of chronic lymphocytic leukemia (CLL), an incurable B-cell malignancy with characteristic dependence on human immune microenvironment. In currently available PDXs proliferation of CLL lymphocytes is maintained by presence of autologous T-cells, however, in few weeks these spontaneously overgrow and eliminate engrafted CLL cells. Our intention is to replace T-cells and supply pro-proliferative and pro-survival signals by their introduction into supportive cell line co-implanted with purified CLL cells. We genetically engineered an adherent supportive cell line, which in coculture induces long term survival and major proliferation of primary CLL cells in vitro. We seeded the cell line on collagen scaffolds, implanted subcutaneously into immunodeficient mice (NSG) and injected highly purified CLL cells (65-350x106 cells per animal). By this we have achieved growth of B-cells in 2 out of 5 transplanted CLL samples; in both cases positive for Epstein- Barr virus (EBNA1 gene). CLL clonal relationship to the patient&apos;s sample was confirmed in one of the grafts by IGHV rearrangement analysis. In this case cells formed a solid tumor positive for CD20/CD45/CD79a cell-surface markers (detected by immunohistochemistry), and cells were found both in peripheral blood and murine spleen, which is a typical site of CLL infiltration in humans. We plan to further assess different ways of transplantation and modify the supportive cells. The established model will be used for testing of novel therapeutic combinations and studies of CLL biology.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů