Human Monocytes - CD14, CD16 - Ziegler-Heitbrock


A phase I study of anti-GD3 ganglioside monoclonal antibody R24 and recombinant human macrophage-colony stimulating factor in patients with metastatic melanoma


BACKGROUND. Macrophages activated by macrophage-colony stimulating factor (M-CSF) are potent immune effector cells and can mediate both in vitro cytotoxicity and antitumor effects in vivo. A Phase I trial combining M-CSF with R24, a mouse monoclonal antibody against GD3 ganglioside that has been shown to localize to melanoma tumors, induce inflammation at tumor sites, and result in major tumor responses in some patients with melanoma was performed. METHODS. Nineteen patients with metastatic melanoma received a 14-day continuous intravenous infusion of 80 micrograms/kg/day of recombinant human M-CSF. R24 was administered daily by intravenous infusion on days 6-10 at doses of 1, 3, 10, 30, and 50 micrograms/m2/day. RESULTS. All patients developed pruritus and urticaria; 13 patients developed transient thrombocytopenia less than 100,000/mm3. The maximum tolerated dose was not reached. All patients developed a monocytosis characterized by increased expression of the antigen HLA-DR and decreased expression of CD14, a phenotype reported to represent a subpopulation of monocytes active in mediating antibody-directed cellular cytotoxicity. Other biologic effects of treatment included marked but transient decreases in total cholesterol, low density lipoprotein, and high density lipoprotein. Three patients experienced tumor regression in breast, liver, and lymph node metastases and received a second course of therapy. Six of the 19 patients, one of whom received no further therapy, survived more than 2 years and 4 of these patients remain alive 24 to 37 months after treatment. Of the six patients with liver metastases, three (50%) survived more than 2.5 years and one remains alive at 37+ months. CONCLUSIONS. Combination therapy with R24 and M-CSF resulted in both clinical and biologic effects that warrant further investigation of this combination.

Authors: Minasian LM, Yao TJ, Steffens TA, Scheinberg DA, Williams L, Riedel E, Houghton AN, Chapman PB
Journal: Cancer 75: 2251
Year: 1995
PubMed: Find in PubMed