Anti-interleukin-2 receptor monoclonal antibody therapy induces anti-idiotypic antibodies in mice that block both in vitro and in vivo activity

Abstract

Monoclonal antibodies (Mab) targeting certain T cell-surface proteins including the interleukin-2 (IL2) receptor molecule exert powerful immunosuppressive effects. A potential limiting factor to Mab therapy is the formation of neutralizing anti-idiotypic antibodies (Anti-Id). In this study, we demonstrate that an anti-IL2 receptor Mab, M7 20 , when administered at doses which are immunosuppressive in vivo rapidly elicits an anti-idiotypic (anti-Id) antibody response. The induced antibodies are capable of blocking M7 20 binding to its target, the IL2 receptor, in vitro. Such anti-Id when given in concert with M7 20 block the expected in vivo inhibitory effects in delayed type hypersensitivity. Thus, mice respond to therapeutic doses of Mab therapy with the formation of neutralizing anti-Id. As this response is similar to that observed in humans given xenogeneic Mab, this model may be useful to further our understanding of this form of therapy.