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Updated: Aug 11, 2026
Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
An orally active, primate selective antagonist of LFA-1 inhibits delayed-type hypersensitivity in a humanized-mouse
Maret J Panzenbeck1, Deborah D Jeanfavre, Terence A Kelly
1Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceutical Inc., 900 Ridgebury Rd., PO Box 368, Ridgefield, CT 06877-0368, USA. mpanzenb@rdg.boehringer-ingelheim.com
Abstract:
Compound I, a novel small molecule antagonist (Kd=6 nM) of human lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) was tested for activity in a humanized mouse model of delayed-type hypersensitivity (trans vivo delayed-type hypersensitivity). Trans vivo delayed-type hypersensitivity is a model for testing compounds with human targets in mice. Tetanus toxoid and 7-10x10(6) human peripheral blood mononuclear cells from tetanus-sensitized donors were coinjected into footpads of naive mice. Footpads were measured before and 24 h later. Injection of peripheral blood mononuclear cells plus antigen resulted in swelling of 0.178-0.254 mm, significantly greater than peripheral blood mononuclear cells or tetanus toxoid alone (P<0.05). Preincubation of peripheral blood mononuclear cells with anti-human major histocompatibility complex class II (MHCII) or anti-human LFA-1 monoclonal antibody (mAb), but not anti-mouse MHCII or anti-mouse LFA-1 mAb, significantly inhibited the response. Compound I inhibited footpad swelling in a dose related manner (0.1-100 mg/kg, p.o.; ED50 approximately 1 mg/kg), whereas its enantiomer had no effect. These data demonstrate the oral efficacy of a novel antagonist of LFA-1 in trans vivo delayed-type hypersensitivity.
