Granulocyte-Macrophage Colony-Stimulating Factor: Pleiotropic Cytokine with Potential Clinical Usefulness

Ruef, C.; Coleman, David L.

doi:10.1093/clinids/12.1.41

Cited by 199 publications

(88 citation statements)

References 208 publications

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“…In vitro experiments suggest the growth and development of the preimplantation embryo is regulated by an array of cytokines and growth factors secreted from epithelial cells lining the oviduct and uterus (16,17). GM-CSF is a cytokine originally identified as a product of activated T-lymphocytes involved in the proliferation and differentiation of myeloid hematopoietic cells (18). In reproductive system, GM-CSF is produced by estrogen-primed epithelial cells in the oviduct and uterus in mice, sheep, and women (5,19,20).…”

Section: Discussionmentioning

confidence: 99%

Preliminary Experience with Low Concentration of Granulocyte-Macrophage Colony-Stimulating Factor: A Potential Regulator in Preimplantation Mouse Embryo Development and Apoptosis

Behr

Mooney

Wen

et al. 2005

J Assist Reprod Genet

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Purpose : To investigate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the development of preimplantation mouse embryos. Methods : Mouse 2-cell embryos were collected and cultured in P-1 medium supplemented with GM-CSF at different concentrations. Using reverse transcription-polymerase chain reaction, expression Bcl-2 and Bax mRNA in blastocyst were evaluated in the GM-CSF group and control group. Apoptosis detection was performed using the in situ apoptosis detection kit in mouse blastocysts. The statistical significance of the data was analyzed using t-test and chi-square test. Results : The development of blastocyst increased to 89% in the addition of GM-CSF (0.125 ng/mL), compared to controlled group (80%). The number of cells staining for apoptosis was lower in GM-CSF group than that in the control group. Bcl-2 expression was found to be upregulated in blastocysts in the GM-CSF supplemented group compared to the control group. Conclusion : These results suggest that GM-CSF might be an important regulator in embryo development.KEY WORDS: Apoptosis; blastocyst development; GM-CSF; in vivo blastocyst.

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Section: Discussionmentioning

confidence: 99%

Preliminary Experience with Low Concentration of Granulocyte-Macrophage Colony-Stimulating Factor: A Potential Regulator in Preimplantation Mouse Embryo Development and Apoptosis

Behr

Mooney

Wen

et al. 2005

J Assist Reprod Genet

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“…GM-CSF was used because of its potent immunostimulating properties and ability to serve as a strong potentiator of tumor vaccines (26 -30). Although our long-term goal is the production of Ab fusion proteins for therapeutic use in humans, human GM-CSF is not active in mice (35). Therefore we used murine GM-CSF in our fusion protein so that we could perform in vivo studies using immune competent mice.…”

Section: Discussionmentioning

confidence: 99%

“…This is consistent with observations with other Ab cytokine fusion proteins (55), demonstrating a dominant role for the attached cytokine in determining the pharmacokinetics of the fusion proteins. We believe that the rapid clearance of the Ab fusion protein is through the GM-CSF receptors on normal cells (35) such as splenic T cells, B cells, and macrophages (56). In fact, our biodistribution studies showed that anti-HER2/neu IgG3-(GM-CSF) is mainly localized in the spleen consistent with earlier reports for the site targeted by murine GM-CSF (57).…”

Section: Discussionmentioning

confidence: 99%

“…Although in vivo gene delivery using viral vectors has been considered, the low transfer efficiency of retroviral vectors and the immunogenicity of adenoviral vectors have limited efficacy (34). Although systemic administration of GM-CSF is an alternative approach, patients in clinical trials receiving high doses of GM-CSF have experienced severe toxic side effects (35) including a reported fatality (36), and no significant antitumor activity has been achieved. Thus, the challenge of developing an effective approach for achieving high local concentrations of GM-CSF remains.…”

Section: T He Her2/neu Protooncogene (Also Known As C-erbb-2)mentioning

confidence: 99%

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

Cruz

Trinh

Morrison

et al. 2000

The Journal of Immunology

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Anti-HER2/neu therapy of human HER2/neu-expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu IgG3 fusion protein containing GM-CSF. Anti-HER2/neu IgG3-(GM-CSF) expressed in myeloma cells was correctly assembled and secreted. It was able to target HER2/neu-expressing cells and to support growth of a GM-CSF-dependent murine myeloid cell line, FDC-P1. The Ab fusion protein activated J774.2 macrophage cells so that they exhibit an enhanced cytotoxic activity and was comparable to the parental Ab in its ability to effect Ab-dependent cellular cytotoxicity-mediated tumor cell lysis. Pharmacokinetic studies showed that anti-HER2/neu IgG3-(GM-CSF) is stable in the blood. Interestingly, the half-life of anti-HER2/neu IgG3-(GM-CSF) depended on the injected dose with longer in vivo persistence observed at higher doses. Biodistribution studies showed that anti-HER2/neu IgG3-(GM-CSF) is mainly localized in the spleen. In addition, anti-HER2/neu IgG3-(GM-CSF) was able to target the HER2/neu-expressing murine tumor CT26-HER2/neu and enhance the immune response against the targeted Ag HER2/neu. Anti-HER2/neu IgG3-(GM-CSF) is able to enhance both Th1- and Th2-mediated immune responses and treatment with this Ab fusion protein resulted in significant retardation in the growth of s.c. CT26-HER2/neu tumors. Our results suggest that anti-HER2/neu IgG3-(GM-CSF) fusion protein is useful in the treatment of HER2/neu-expressing tumors.

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“…The GM-CSF is a lymphohemopoietic factor synthesized in uterus of non pregnant mouse (peak in estrus) and maintained at comparable or moderately higher level during the preimplantation period of pregnancy [23]. Epithelium of uterine and oviduct is the major site of GM-CSF secretion [24] and its targets in this site are myeloid leukocytes, pre-implantation embryo and trophoblast cells [25,26].…”

Section: Introductionmentioning

confidence: 99%

Developmental potential of isolated blastomeres from early mouse embryos in the presence and absence of LIF and GM-CSF

Sheikholslami

Salehnia

Valojerdi

et al. 2008

J Assist Reprod Genet

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Purpose The aim of this study was to investigate the developmental potential of isolated blastomeres in the presence and absence of leukemia inhibitory factor (LIF) and granulocyte-macrophage colony stimulating factor (GM-CSF). Methods The blastomeres of two (1/2) and eight cells (1/8) embryos were isolated and cultured in T6 medium in the presence and absence of LIF (1,000 IU/ml) and or GM-CSF (2 ng/ml) up to 120 h. The diameter and cell number of blastocysts were measured. Results The developmental rates of 1/2 isolated blastomeres developed to blastocysts stages in the presence and absence of LIF and GM-CSF were 45.80, 35.10 and 48.66, 41.66, respectively. The diameter of blastocysts was higher in GM-CSF group and total cell number of blastocyst in both treated groups was higher than control (P<0.05). No 1/8 blastomeres developed to morula and blastocyst stages. Conclusions LIF and GM-CSF could improve the development of 1/2 isolated blastomeres.

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Granulocyte-Macrophage Colony-Stimulating Factor: Pleiotropic Cytokine with Potential Clinical Usefulness

Cited by 199 publications

References 208 publications

Preliminary Experience with Low Concentration of Granulocyte-Macrophage Colony-Stimulating Factor: A Potential Regulator in Preimplantation Mouse Embryo Development and Apoptosis

Preliminary Experience with Low Concentration of Granulocyte-Macrophage Colony-Stimulating Factor: A Potential Regulator in Preimplantation Mouse Embryo Development and Apoptosis

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

Developmental potential of isolated blastomeres from early mouse embryos in the presence and absence of LIF and GM-CSF

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