IN-VIVO EFFECTS OF PURIFIED RECOMBINANT HUMAN MACROPHAGE-COLONY-STIMULATING FACTOR IN COMBINATION WITH LOCAL HYPERTHERMIA ON TUMOR PROGRESSION IN B16A-MELANOMA BEARING MICE

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) w as evaluated, alone or in combination with local hyperthermia (LH), fo r their antitumor effects in mice inoculated with B16a melanoma cells. Several tumor related parameters and other hematopoietic and immunolo gic parameters were evaluated 5 weeks after subcutaneous (s.c.) inocul ation of tumor cells into the right limbs of C57BL/6J male mice. RhuM- CSF was administered at 20 mug/injection, s.c., twice a day for 5 days /week for 2 weeks beginning 6 days after tumor cell inoculation and LH (43 +/- 0.2-degrees-C) was given for 30 min twice/week for 2 weeks. C ombined therapy prolonged survival of mice and caused significant inhi bition of tumor growth, as measured by the volume or size of primary t umor, number and size of lung metastases, and chromatin fragment (CF) formation in tumor bearing mice, while treatment with M-CSF or LH alon e had less or no effect. Combined therapy also resulted in increased n umbers of splenic T-lymphocytes and the ratio of T-helper/suppressor c ells, restoration of natural killer (NK) cell activity, increased numb ers of peritoneal macrophages and their erythrophagocytosis capacity, and increased release or production of tumor necrosis factor (TNF)-alp ha, but not interleukin (IL)-1alpha or IL-6. These results add to prev ious evidence that M-CSF might be a relevant therapeutic agent in comb ination with other therapies in the treatment of certain malignant dis eases.