title: Evaluation of antigen-based heteropolymer for treatment of systemic lupus erythematosus in a nonhuman primate model.
abstract: Autoantibodies that react with double-stranded DNA (dsDNA) are a hallmark for diagnosis of systemic lupus erythematosus (SLE) and are also considered the pathogenic subset that is most associated with lupus nephritis. As an agent to remove the pathogenic dsDNA antibodies from the circulation of SLE patients, we are developing an antigen-based heteropolymer (AHP). The AHP consists of a monoclonal antibody to the complement receptor (CR1) cross-linked to salmon testis dsDNA to effect clearance of anti-DNA antibodies by binding them to erythrocyte CR1. Utilizing a cynomolgus monkey model for SLE in which we infused plasma from SLE patients containing a high titer of high-avidity anti-dsDNA antibody, we have evaluated the safety and efficacy of AHP infusion. The results demonstrate that AHP rapidly (within 2 min of infusion) binds to monkey erythrocytes without causing any toxicological effects. We also demonstrate that human Ig (G+M) antibodies are rapidly bound to the AHP-erythrocyte complex. These events are mirrored in their kinetics by a substantial drop in the level of high-avidity dsDNA antibody in the plasma.
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey 07058, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Pincus
authors.forename: Nadya
authors.initials: N
authors.lastname: Lukacher
authors.forename: Nehal
authors.initials: N
authors.lastname: Mohamed
authors.forename: Muctarr
authors.initials: M
authors.lastname: Sesay
authors.forename: Roger
authors.initials: R
authors.lastname: Zabinski
authors.forename: Rose
authors.initials: R
authors.lastname: Ebelle
authors.forename: Lisa
authors.initials: L
authors.lastname: Duncan
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Xun
authors.initials: X
authors.lastname: Chen
authors.forename: Wu
authors.initials: W
authors.lastname: Peng
authors.forename: Josaih
authors.initials: J
authors.lastname: Adaelu
authors.forename: Leslie
authors.initials: L
authors.lastname: Casey
authors.forename: James P
authors.initials: JP
authors.lastname: Porter
authors.forename: George
authors.initials: G
authors.lastname: Spitalny
authors.forename: Linda L
authors.initials: LL
authors.lastname: Nardone
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000915:Antibody Affinity; D000941:Antigens; D004247:DNA / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D008252:Macaca fascicularis; D008297:Male; D017463:Receptors, Complement 3b / Q000276:immunology; D012474:Salmon
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000941:Antigens; D017463:Receptors, Complement 3b; D004247:DNA