Monoclonal anti-TNF-α suppresses graft vs host disease reactions in an in vitro human skin model

Abstract

Graft vs host disease (GVHD) following allogeneic marrow transplant in humans is known to be mediated in part by cytokines. Tumour necrosis factor α (TNF-α) and gamma interferon (IFN-γ) are considered to be critical in the mechanism. A commercially produced antibody to TNF-α (CB0006) was tested in vitro to assess its ability to suppress mixed lymphocyte reactions (MLR). Peripheral blood mononuclear cells treated and untreated with CB0006 were also tested for their ability to elicit a graft vs host reaction (GVHR) in vitro in a human skin-explant model for GVHD. The results showed that CB0006 could inhibit mixed lymphocyte culture (MLC) proliferative responses and that in vitro antibody treated responder cells were less effective in causing GVHR in vitro skin-explant assays. CB0006 was also shown to inhibit MLC supernatant induced GVHR.