| Abstract |
By being a model organism, dog fills the gap between the research
conducted on mice and on patients very well due to the similarities of the
development and course of cancer. Cell lines established from the primary
cancer cells are a convenient tool for the fast and efficient screenings
of new therapeutic approaches. Currently, many canine cancer cell lines
are available, including those arising from type B and type T leukemias
and lymphomas, however up to date no canine natural killer (NK) cell line
was characterized. NK cells can kill cancer and viral-infected cells
without prior immunization which is recently used for designing
immunotherapeutic approaches. The aim of this project was to characterize
phenotypically and functionally new cell line arising from a canine cancer
which was initially evaluated as a NK-type. Experiments included in this
thesis proved that a new cell line CNK-89 displays the phenotype of NK
cells: the presence of CD5, CD8, CD45, CD56, NKp46 and CD79a proteins as
well as the transcripts for CD56, NKG2D, NKp30, NKp44, NKp46 and perforin
genes. Functionally, CNK-89 cells showed cytotoxicity against canine B-
type leukemia/lymphoma cells. Priming of CNK-89 cells with interleukins IL-
12 and IL-18 for 48 hours increased their cytotoxic properties and this
effect was still visible after 7 days from interleukins removal. The
characteristics of CNK-89 cells performed in this project can contribute
to the development of the research focused on canine immunotherapies which
in turn may be beneficial to the therapies for human cancers.
|