Granulocyte-macrophage colony-stimulating factor-producing tumour vaccines

Murine sarcoma MC12 cells were transfected with the gene coding for murine granulocyte-macrophage colony-stimulating factor (GM-CSF), Tumorigenicity o f a variety of cell clones with different expression of the inserted gene w as assessed. All of the genetically manipulated MC12 cell clones examined w ere found to be less tumorigenic than the parental MC12 cell population. No correlation was observed between the production of GM-CSF by the clones an d their tumorigenicity, It has been found that irradiation of the GM-CSF-pr oducing cells with the dose of 150 Gy did not significantly inhibit the GM- CSF production during the period of 5 days after irradiation, These finding s provided us with the rationale for using the irradiated GM-CSF-producing MC12 sarcoma vaccine for therapy. It has further been found than immunosens itivity of the genetically manipulated, GM-CSF-producing tumour targets to the IL-2-activated killer (LAK) cell-mediated cytolysis was significantly i ncreased, as compared to the parental target cell population. Irradiated, G M-CSF-producing tumour vaccines were used for therapy of 3-day-old MC12 sar coma transplants in syngeneic mice and for therapy of surgically induced mi nimal residual tumour disease. Neither small tumour transplants, nor tumour residua after surgery were significantly sensitive to the therapy with GM- CSF-producing tumour vaccines.