Antibody-independent phagocytosis of tumor cells by human monocyte-derived macrophages cultured in recombinant macrophage colony-stimulating factor

1995 ◽  
Vol 41 (1) ◽  
pp. 46-52 ◽  
Author(s):  
David H. Munn ◽  
Nai-Kong V. Cheung
Keyword(s):  
Tumor Cells ◽  
Human Monocyte ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

In vivo effects of macrophage colony-stimulating factor on human monocyte function

1991 ◽  
Vol 77 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Asim Khwaja ◽  
Beryl Johnson ◽  
Ian E. Addison ◽  
Kwee Yong ◽  
Karen Ruthven ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Colony Stimulating Factor ◽  
Monocyte Function ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
In Vivo Effects ◽  
Stimulating Factor

Vaccination With Irradiated, Autologous Melanoma Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor by Adenoviral-Mediated Gene Transfer Augments Antitumor Immunity in Patients With Metastatic Melanoma

2003 ◽  
Vol 21 (17) ◽  
pp. 3343-3350 ◽  
Author(s):  
Robert Soiffer ◽  
F. Stephen Hodi ◽  
Frank Haluska ◽  
Ken Jung ◽  
Silke Gillessen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Melanoma Cells ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Purpose: Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer.Patients and Methods: Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1 × 106, 4 × 106, or 1 × 107tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals.Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/106cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease.Conclusion: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.

scholarly journals Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages.

1987 ◽  
Vol 166 (5) ◽  
pp. 1436-1446 ◽  
Author(s):  
W Y Weiser ◽  
A Van Niel ◽  
S C Clark ◽  
J R David ◽  
H G Remold
Keyword(s):  
Leishmania Donovani ◽  
Human Monocyte ◽  
Peripheral Blood Monocyte ◽  
Antileishmanial Activity ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) obtained from cloned complementary Mo cell DNA and expressed in COS-1 cells activates cultured peripheral blood monocyte-derived macrophages in vitro to become cytotoxic for intracellular L. donovani. The antileishmanial effect of rGM-CSF, which can be completely neutralized by anti-rGM-CSF antiserum, is maximal after 36 h preincubation with the cultured macrophages, compared with that of rIFN-gamma, which reaches its maximum at 72 h of preincubation. The antileishmanial effect of GM-CSF as well as IFN-gamma is independent of detectable amounts of LPS and is not augmented by the addition of 10 or 50 ng/ml of LPS. Simultaneous administration of suboptimal doses of rGM-CSF and rIFN-gamma to monocyte-derived macrophages results in greater antileishmanial activity by these cells than administration of either lymphokine alone, although no enhancement of antileishmanial activity is observed when optimal doses of these two lymphokines are applied together.

scholarly journals Critical Prosurvival Roles for C/EBPβ and Insulin-Like Growth Factor I in Macrophage Tumor Cells

2004 ◽  
Vol 24 (8) ◽  
pp. 3238-3250 ◽  
Author(s):  
Jennifer Wessells ◽  
Shoshana Yakar ◽  
Peter F. Johnson
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Insulin Like Growth Factor ◽  
Colony Stimulating Factor ◽  
Factor I ◽  
Survival Factor ◽  
Igf I ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT One of the hallmarks of leukemic cells is their ability to proliferate and survive in the absence of exogenous growth factors (GFs). However, the molecular mechanisms used by myeloid tumor cells to escape apoptosis are not fully understood. Here we report that Myc/Raf-transformed macrophages require the transcription factor C/EBPβ to prevent cell death. In contrast to wild-type cells, C/EBPβ−/− macrophages were completely dependent on macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor for survival and displayed impaired tumorigenicity in vivo. Microarray analysis revealed that C/EBPβ-deficient cells expressed significantly reduced levels of the prosurvival factor insulin-like growth factor I (IGF-I). Overexpression of C/EBPβ stimulated transcription from the IGF-I promoter, indicating that IGF-I is a direct transcriptional target of C/EBPβ. Serological neutralization of IGF-I in C/EBPβ+/+ tumor cell cultures induced apoptosis, showing that IGF-I functions as an autocrine survival factor in these cells. Macrophage tumor cells derived from IGF-I−/− mice were GF dependent, similar to C/EBPβ-deficient cells. Forced expression of either C/EBPβ or IGF-I in C/EBPβ−/− bone marrow cells restored Myc/Raf-induced transformation and permitted neoplastic growth without exogenous GFs. Thus, our findings demonstrate that C/EBPβ is essential for oncogenic transformation of macrophages and functions at least in part by regulating expression of the survival factor IGF-I.

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