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

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-alpha, 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. (C) 2011 Elsevier B.V. All rights reserved.