ANTITUMOR EFFECTS OF RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR, ALONE OR IN COMBINATION WITH LOCAL IRRADIATION, IN MICE INOCULATED WITH LEWIS LUNG-CARCINOMA CELLS

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated for efficacy, either alone or in combination with local X-irradiation (LR), in mice inoculated subcutaneously (s.c.) with Lewis lung carcinoma (LLC) cells. The size of the primary tumor and numbers of lung metastases, 21 days after tumor inoculation and 15 days after the start of treatment, were reduced by 87% in tumor-bearing mice treated with 20-mu-g/dose M-CSF s.c. twice a day for 5 days. LR (800 cGy) to the tumor once a week for 2 weeks had a moderate anti-tumor effect and enhanced the anti-tumor effect of M-CSF. Hematological parameters, including nucleated cellularity in peripheral blood, femoral marrow, spleen and peritoneal exudate, as well as marrow and splenic granulocyte-macrophage progenitor cells, and numbers of splenic Thy1.2+ cell and peritoneal mast cells, were perturbed in LLC-bearing mice, and were influenced by treatment with M-CSF and LR. Treatment with M-CSF plus LR, but not with either agent alone, was associated with a significant, although slight, enhancement in survival time for LLC-bearing mice. Inability to obtain a better survival-enhancing effect appeared to be related to the limited treatment, since the anti-tumor effects of M-CSF were more notable early on in disease progression and were related to the dose of M-CSF used. The effects of M-CSF were most probably indirect ones on the host immune system. M-CSF, in combination with LR, may be of benefit in the treatment of human tumors that have metastatic potential.