Antigens pre‐bound to the primate erythrocyte complement receptor via cross‐linked bispecific monoclonal antibody heteropolymers are rapidly cleared from the circulation

Reist, Craig J.; Combs, Matthew J.; Croft, Barbara Y.; Taylor, Ronald P.

doi:10.1002/eji.1830231144

Cited by 16 publications

(13 citation statements)

References 39 publications

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“…Next, ICs are cleared from liver or spleen (Davies et al 1990). Transfer of the ICs to liver or spleen phagocytes leads to IC destruction but generally occurs without harm to the erythrocytes that are recycled (Birmingham and Hebert 2001;Cosio et al 1981;Cosio, Sedmak, and Nahman 1990;Hebert, Birmingham, Mahan, et al 1994;Reist et al 1993).…”

Section: Ic Clearance Mechanismsmentioning

confidence: 99%

“…Experimentally, cross-linked mAb complexes (e.g., bispecific antibodies that recognize CR1 as well as an unrelated antigen) also bind to CR1 for clearance by liver and spleen phagocytic cells (Edberg, Kimberly, and Taylor 1992;Nardin, Lindorfer, and Taylor 1999;Reist et al 1993;Taylor et al 1992;Taylor, Ferguson, et al 1997). IgG dimers present in therapeutic intravenous immunoglobulin (IVIg) drugs also activate complement, acquire C3b deposits, and bind to CR1 (Shoham-Kessary, Naot, and Gershon 1998).…”

Section: Ic Clearance Mechanismsmentioning

confidence: 99%

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Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.

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Section: Ic Clearance Mechanismsmentioning

confidence: 99%

Section: Ic Clearance Mechanismsmentioning

confidence: 99%

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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“…Previously, we reported that "partial heteropolymers," biotinylated anti-CR1 MAb mixed with SA, bind in vivo to erythrocytes of rhesus monkeys but are not cleared from the circulation (25). However, complete heteropolymers, containing MAb to CR1 cross-linked with either human or mouse IgG, bind to primate erythrocytes and are cleared (26). Numerous in vivo studies indicate that IgG that is bound to erythrocytes via cell surface antigens causes the erythrocyte to be recognized and cleared by the RES (45,46), yet IgG that is bound to erythrocyte CR1 as part of a C3b-opsonized IC does not sensitize erythrocytes for clearance, but IC are cleared and removed from erythrocytes in the liver and spleen (19,20).…”

Section: Discussionmentioning

confidence: 99%

“…MAb 1B4 (also anti-CR1) and HB43 (anti-human IgG) have been characterized previously (3 1-33). Anti-CRl MAb were conjugated with biotin at combining molar ratios of 10 biotins per MAb (26,34). MAb were labeled with 1251 by the iodogen method (35).…”

Section: Methodsmentioning

confidence: 99%

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Antigen‐based heteropolymers: a potential therapy for binding and clearing autoantibodies via erythrocyte cr1

Ferguson

Reist

Martin

et al. 1995

Arthritis & Rheumatism

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Objective. To determine if complexes containing monoclonal antibodies to CR1 cross-linked with antigen (antigen-based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation.Methods. AHP were constructed by cross-linking double-stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti-dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence-activated cell sorting. In addition, we used a monkey model to study in vivo the AHP-mediated clearance of passively infused human anti-dsDNA an ti bodies.Results. Large amounts of lupus IgG anti-dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation.Conclusion. This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.Antinuclear antibodies have been recognized as a serologic hallmark of systemic lupus erythematosus

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Cross‐linked bispecific monoclonal antibody heteropolymers facilitate the clearance of human IgM from the circulation of squirrel monkeys

et al. 1994

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We have previously demonstrated that cross-linked bispecific monoclonal antibodies (mAb) heteropolymers (HP), specific for primate erythrocyte (E) complement receptor type 1 (CR1) and target antigen (Ag), facilitate the binding of these target Ag to human and non-human primate E. Once bound in vitro to rhesus monkey E, upon re-infusion these HP/Ag complexes are recognized in vivo by cells of the reticuloendothelial system (RES) and removed from the circulation without loss of the E. We now show, in squirrel monkeys, that an HP specific for E CR1 and human IgM (anti-CR1 x anti-IgM) can be used to facilitate in vivo E binding and clearance from the circulation of a previously injected and circulating model protein pathogen, human IgM. Approximately 70-80% of 125I-labeled human IgM is cleared from the circulation of each of five squirrel monkeys via the HP system. We observe, in experiments analogous to previous studies on immune complex (IC) clearance, that subsequent to HP/Ag clearance there is a decrease in the number of CR1 epitopes per E which is manifested when we use both monoclonal and polyclonal anti-CR1 probes. Our results indicate that the primary organs responsible for uptake of the complexes are the liver and spleen. This work strongly suggests that the HP/Ag complexes, bound to E, function as IC prototypes and are recognized and processed as such in vivo. Thus, the HP-E system may eventually serve as a viable immunotherapy for the clearance of blood-borne pathogens from the circulation.

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Antigens pre‐bound to the primate erythrocyte complement receptor via cross‐linked bispecific monoclonal antibody heteropolymers are rapidly cleared from the circulation

Cited by 16 publications

References 39 publications

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

Antigen‐based heteropolymers: a potential therapy for binding and clearing autoantibodies via erythrocyte cr1

Cross‐linked bispecific monoclonal antibody heteropolymers facilitate the clearance of human IgM from the circulation of squirrel monkeys

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