Elsevier

Cytokine

Volume 7, Issue 3, April 1995, Pages 251-259
Cytokine

Regular article
Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions

https://doi.org/10.1006/cyto.1995.0029Get rights and content

Abstract

Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4+T cells and macrophages, cells known to express transmembrane TNF-α upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-α and what effects such binding may have on TNF-α-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-α was prepared for these studies. Analysis of these TNF+cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-α with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF+cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane TNF-α in vitro and suggest that cA2 binding may lead to lysis of TNF-α-expressing cells in vivo.

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