title: 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: Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire EN6 3QG, UK. lucy.findlay@nibsc.hpa.org.uk
authors: Lucy
authors: L
authors: Findlay
authors: David
authors: D
authors: Eastwood
authors: Christina
authors: C
authors: Ball
authors: C Jane
authors: CJ
authors: Robinson
authors: Chris
authors: C
authors: Bird
authors: Meenu
authors: M
authors: Wadhwa
authors: Susan J
authors: SJ
authors: Thorpe
authors: Robin
authors: R
authors: Thorpe
authors: Richard
authors: R
authors: Stebbings
authors: Stephen
authors: S
authors: Poole
mesh_terms: D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D042783:Endothelial Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007167:Immunotherapy / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D007262:Infusions, Intravenous; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D012307:Risk Factors
chemical_list: D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators