Geneticky modifikované buněčné vakcíny proti bcr-abl-transformovaným buňkám

• Main Author: Petráčková, Martina
• Other Authors: Vonka, Vladimír
• Format: Doctoral Thesis
• Language: Czech
• Published: 2012
• Online Access: http://www.nusl.cz/ntk/nusl-322654

of PhD. Thesis Gene Modified Cellular Vaccines against bcr-abl-Transformed Cells In our laboratory we are focused on the development of therapeutic vaccines against chronic myeloid leukaemia (CML), using as a model system mouse bcr-abl-transformed B210 and 12B1 cells. Both these cells are of early B-cell lineage, express BCR-ABL protein and induce leukaemia after i.v. inoculation; the 12B1 cells also induce solid lymphoma-like tumours after s.c. inoculation. Several types of experimental vaccines directed against these bcr-abl-transformed cells were developed in our laboratory. Since it has been recognized that BCR-ABL protein does not carry the immunodominant epitope, our attention switched to the development of cell-based vaccines that are capable of inducing immune responses against a whole complex of tumour-associated antigens. The present work describes studies on experimental cellular vaccines based on the B210 or 12B1 cells, gene-modified to express either IL-2 or GM-CSF or IL-12. For the transfection of these cells, an optimised electroporation method was used. The vaccines were tested in our mouse BALB/c model. All the cell lines derived from B210 cells secreting IL-2, GM-CSF or IL-12 were non-oncogenic. The oncogenicity of the IL-2 producing 12B1 sublines was reduced and most of the...