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Granulocyte-macrophage colony stimulating factor (GM-CSF) is consideredto be the most effective immunostimulating factor for the construction of gene-engineeredanti-cancer vaccines. In some tumour cells, this type of genetic modificationhas resulted in the loss of the oncogenic potential. This was not the case withbcr-abl-transformed mouse 12B1 cells. A cell line, designated 12B1/GM-CSF/cl-5producing more than 100 ng/106 cells/24 h, displayed higher pathogenicity thanthe parental, non-transduced cells. Although the tumours induced by the parental12B1 cells and 12B1/GM-CSF/cl-5 cells appeared nearly at the same time and thengrew at an approximately equal rate, the latter mice were in a much poorer clinicalcondition. In these animals the growth of the tumours was associated with graduallyincreasing blood levels of GM-CSF. In both groups of animals splenomegaly wasobserved; it was much more pronounced in the case of 12B1/GM-CSF/cl-5-inoculatedanimals. While in the case of animals inoculated with the parental cells the splenomegalywas probably mainly due to infiltration with tumour cells, in the animals inoculatedwith the GM-CSF-secreting cells splenomegaly and derangement of parenchymal organs,such as lungs, liver and kidneys, were more complex, including congestion andinfiltration with hemopoietic cells, predominantly immature cells of myeloid lineage.The most conspicuous of these changes was the hyperaemia of the lungs. No suchalterations were seen in animals inoculated with the parental cells. On the otherhand, the contents of T regulatory cells were comparable in both groups and theyincreased in parallel at the end of the observation period. When GM-CSF neutralizingantibody was administered to animals inoculated with the 12B1/GM-CSF/cl-5 cells,the pathological changes observed within the organs were suppressed, this provingthat the overproduced GM-CSF and not any other substance, played the key rolein their induction.

international journal of oncology

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