title: Properties of bcr-abl-transformed mouse 12B1 cells secreting interleukin-2             and granulocyte-macrophage colony stimulating factor (GM-CSF): II. Adverse effects             of GM-CSF.
abstract: Granulocyte-macrophage colony stimulating factor (GM-CSF) is considered             to be the most effective immunostimulating factor for the construction of gene-engineered             anti-cancer vaccines. In some tumour cells, this type of genetic modification             has resulted in the loss of the oncogenic potential. This was not the case with             bcr-abl-transformed mouse 12B1 cells. A cell line, designated 12B1/GM-CSF/cl-5             producing more than 100 ng/106 cells/24 h, displayed higher pathogenicity than             the parental, non-transduced cells. Although the tumours induced by the parental             12B1 cells and 12B1/GM-CSF/cl-5 cells appeared nearly at the same time and then             grew at an approximately equal rate, the latter mice were in a much poorer clinical             condition. In these animals the growth of the tumours was associated with gradually             increasing blood levels of GM-CSF. In both groups of animals splenomegaly was             observed; it was much more pronounced in the case of 12B1/GM-CSF/cl-5-inoculated             animals. While in the case of animals inoculated with the parental cells the splenomegaly             was probably mainly due to infiltration with tumour cells, in the animals inoculated             with the GM-CSF-secreting cells splenomegaly and derangement of parenchymal organs,             such as lungs, liver and kidneys, were more complex, including congestion and             infiltration with hemopoietic cells, predominantly immature cells of myeloid lineage.             The most conspicuous of these changes was the hyperaemia of the lungs. No such             alterations were seen in animals inoculated with the parental cells. On the other             hand, the contents of T regulatory cells were comparable in both groups and they             increased in parallel at the end of the observation period. When GM-CSF neutralizing             antibody was administered to animals inoculated with the 12B1/GM-CSF/cl-5 cells,             the pathological changes observed within the organs were suppressed, this proving             that the overproduced GM-CSF and not any other substance, played the key role             in their induction.
authors.affiliation: Department of Experimental Virology, Institute of Hematology                     and Blood Transfusion, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Petráčková
authors.forename: Libor
authors.initials: L
authors.lastname: Staněk
authors.forename: Václav
authors.initials: V
authors.lastname: Mandys
authors.forename: Pavel
authors.initials: P
authors.lastname: Dundr
authors.forename: Vladimír
authors.initials: V
authors.lastname: Vonka
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D045744:Cell Line, Tumor; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D007938:Leukemia / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D047368:Tumor Burden
chemical_list: D057134:Antibodies, Neutralizing; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl