Comparison of novel methods for predicting the risk of pro-inflammatory clinical infusion reactions during monoclonal antibody therapy.

Abstract

Two methods for predicting the risk of pro-inflammatory clinical infusion reactions during monoclonal antibody therapy were evaluated. In the first, the antibody of interest is immobilised by air-drying onto 96-well plates prior to the addition of human peripheral blood mononuclear cells (PBMCs). In the second, the antibody is added in aqueous phase to a co-culture of human PBMCs and human endothelium-derived cells. In both methods the cells are incubated with the antibody to allow the accumulation of pro-inflammatory cytokines, quantified by enzyme-linked immunosorbent assay (ELISA). The antibodies associated with clinical infusion reactions, Herceptin, Campath-1H and TGN1412, gave the largest responses taking into account the data for all readouts (tumour necrosis factor-α, TNF, interleukin-6, IL-6, IL-8, IL-2 and cell proliferation) for both methods. Overall, the antibodies tested could be ranked as follows: Tysabri<Avastin<Herceptin<Campath-1H<TGN1412, with only the "superagonistic" CD28 monoclonal antibody (TGN1412) stimulating IL-2 release and cell proliferation.

• Authors: Lucy Findlay, David Eastwood, Christina Ball, C Jane Robinson, Chris Bird, Meenu Wadhwa, Susan J Thorpe, Robin Thorpe, Richard Stebbings, Stephen Poole
• Journal: Journal of immunological methods (J Immunol Methods) Vol. 371 Issue 1-2 Pg. 134-42 (Aug 31 2011) ISSN: 1872-7905 [Electronic] Netherlands
• PMID: 21741383 (Publication Type: Comparative Study, Evaluation Study, Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Immobilized
• Antibodies, Monoclonal
• Cytokines
• Inflammation Mediators

Topics

• Antibodies, Immobilized
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Cell Proliferation
• Coculture Techniques
• Cytokines (analysis, biosynthesis)
• Endothelial Cells (immunology)
• Enzyme-Linked Immunosorbent Assay (methods)
• Humans
• Immunoassay (methods)
• Immunotherapy (adverse effects)
• Inflammation (etiology, immunology)
• Inflammation Mediators (analysis, metabolism)
• Infusions, Intravenous
• Leukocytes, Mononuclear (immunology, pathology)
• Risk Factors