Evaluation of antigen-based heteropolymer for treatment of systemic lupus erythematosus in a nonhuman primate model.
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.
Pincus
Steven E
SE
Elusys Therapeutics, Inc., Pine Brook, New Jersey 07058, USA.
Lukacher
Nadya
N
Mohamed
Nehal
N
Sesay
Muctarr
M
Zabinski
Roger
R
Ebelle
Rose
R
Duncan
Lisa
L
Li
Juan
J
Chen
Xun
X
Peng
Wu
W
Adaelu
Josaih
J
Casey
Leslie
L
Porter
James P
JP
Spitalny
George
G
Nardone
Linda L
LL
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
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000941:Antigens; D017463:Receptors, Complement 3b; D004247:DNA