Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Advanced Malignancy: A Phase Ib Trial

Abstract

We evaluated the toxic, hematopoietic, and immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). The rHuGM-CSF was administered at doses up to 50 micrograms/kg by daily 2-hour intravenous infusions to 11 patients with advanced malignancy. It induced dose-related increases in cells of the myeloid series, but it had no significant effect on reticulocyte or platelet counts. Bone marrow cellularity increased with higher doses of rHuGM-CSF, but there was a dose-related decrease in the number of colony-forming units--granulocyte-monocyte--and colony-forming units--granulocyte-erythrocyte-monocyte-megakaryocyte--per 10(5) bone marrow cells. The rHuGM-CSF caused transient increased expression of CD11b and CD16 on granulocytes but increased expression of HLA-DR and decreased expression of the high-affinity Fc receptor on monocytes and no change in monocyte production of H2O2. Thus, rHuGM-CSF has potent effects on granulocyte, eosinophil, and monocyte numbers in the peripheral blood and bone marrow. In addition, it enhances the expression of monocyte and granulocyte activation-associated surface markers.

Cytotoxic functions of blood mononuclear cells in patients with colorectal carcinoma treated with mAb 17-1A and granulocyte/macrophage-colony-stimulating factor

“…Kleinerman et al [18] observed no activation of monocyte cytotoxicity after GM-CSF administration nor could Steis et al [36] notice increased production of H202 (measurement of monocyte activation) after stimulation with phorbol myristate acetate. The augmented spontaneous cytotoxicity noticed in the present study is thus probably due to activation of lymphocyte subsets.…”

GM-CSF plus rituximab immunotherapy: Translation of biologic mechanisms into therapy for indolent B-cell lymphomas

“…The therapeutic potential of GM-CSF stems from numerous in vitro and ex vivo studies dating back to the 1980s. These studies demonstrated a complex interplay of mechanisms, including promotion of monocytes to macrophage differentiation, enhanced surface molecule expression and cytotoxic effects (Table II) [45,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62].…”

“…Steis et al showed that 1-50 mg/kg recombinant human GM-CSF increased the absolute number of neutrophils, eosinophils, lymphocytes and monocytes in patients with solid tumors [52]. The increase in granulocytic cells (neutrophils and eosinophils) can be associated with anti-viral-and anti-inflammatory-related effects, as well as enhanced phagocytosis.…”

Recombinant Anti-Human HER2/neuIgG3-(GM-CSF) Fusion Protein Retains Antigen Specificity and Cytokine Function and Demonstrates Antitumor Activity

“…It is also a potent immunostimulator with pleiotropic effects, including the augmentation of Ag presentation in a variety of cells (17)(18)(19)(20)(21)(22), increased expression of MHC class II on monocytes and adhesion molecules on granulocytes and monocytes (23)(24)(25), and amplification of T cell proliferation (26). In animals, the injection of GM-CSF potentiates the protective effects of an antitumor vaccine by enhancing T cell immunity (26), and vaccination with GM-CSF-transduced cells has been shown to be effective in the treatment of experimental tumors in murine models (27)(28)(29)(30).…”