NDLI: Production of neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in carcinoma patients following GM-CSF combination therapy

Content Provider	PubMed Central
Author	Wadhwa, M. Bird, C. Fagerberg, J. Gaines-das, R. P, Ragnhammar H, Mellstedt Thorpe, R.
Copyright Year	1996
Abstract	In this study, the development of neutralizing and non-neutralizing GM-CSF antibodies and the clinical consequences related to the induction of these antibodies were analysed in 20 patients with metastatic colorectal carcinoma receiving a combination therapy of Escherichia coli-derived GM-CSF and a colon carcinoma-reactive MoAb in the absence of any concomitant chemotherapy. The recombinant human GM-CSF was administered subcutaneously for 10 days every month for 4 months. Following the first cycle of treatment, no GM-CSF antibodies were detected, but during subsequent therapy, 19 of the 20 patients studied developed GM-CSF binding antibodies. However, only a proportion (40%) of the 19 antibody-positive patients developed antibodies that neutralized the biological activity of GM-CSF in an in vitro bioassay. The presence of GM-CSF neutralizing antibodies was associated with a significant reduction in GM-CSF-induced expansion of leucocytes, neutrophils and eosinophils. Such clinical effects were not apparent in patients with non-neutralizing antibodies. Further characterization of sera from patients with neutralizing antibodies showed that, in most cases, the antibodies neutralized the biological activity of GM-CSF preparations derived using different expression systems (chinese hamster ovary cells and yeast), suggesting that these antibodies may have the potential to cross-react with endogenously produced GM-CSF. These effects should be considered before therapeutic use of cytokines, particularly in patients who are not immunosuppressed, and therefore capable of mounting an effective immune response. Our results indicate that assessment of production of neutralizing antibodies induced during cytokine therapy can be used to predict diminished clinical response to further therapy.
Related Links	http://dx.doi.org/10.1046/j.1365-2249.1996.11704.x
Ending Page	358
Page Count	8
Starting Page	351
File Format	PDF
ISSN	00099104
e-ISSN	13652249
Journal	Clinical and Experimental Immunology
Issue Number	2
Volume Number	104
Language	English
Publisher	Blackwell Science Inc
Publisher Date	1996-05-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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