Kupffer cell depletion<i>in vivo</i>results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells

Bogers, Willy; Stad, Robert; Janssen, D. J.; Rooijen, Nico van; Es, Leendert A. van; Daha, Mohamed R.

doi:10.1111/j.1365-2249.1991.tb05818.x

Cited by 38 publications

(9 citation statements)

References 22 publications

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“…These results support the presence of circulating ADAs in pretreated mice that upon retreatment form drug/anti-drug ICs. Then, the ICs likely undergo rapid fragment-crystallizable gamma receptor-mediated hepatic clearance and degradation as previously shown by others (Bogers et al, 1991;Løvdal et al, 2000;Ganesan et al, 2012). The efficient removal of potential ICs is in agreement with the low levels of circulating DTA-1 containing HMW complexes in pretreated mice as shown in Fig.…”

Section: Resultssupporting

confidence: 65%

The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice

Brunn

Mauze

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Administration of biologics to enhance T-cell function is part of a rapidly growing field of cancer immunotherapy demonstrated by the unprecedented clinical success of several immunoregulatory receptor targeting antibodies. While these biologic agents confer significant anti-tumor activity through targeted immune response modulation, they can also elicit broad immune responses potentially including the production of anti-drug antibodies (ADAs). DTA-1, an agonist monoclonal antibody against GITR, is a highly effective anti-tumor treatment in preclinical models. We demonstrate that repeated dosing with murinized DTA-1 (mDTA-1) generates ADAs with corresponding reductions in drug exposure and engagement of GITR on circulating CD31 CD4 1 T cells, due to rapid hepatic drug uptake and catabolism. Mice implanted with tumors after induction of preexisting mDTA-1 ADA show no anti-tumor efficacy when given 3 mg/kg mDTA-1, an efficacious dose in naive mice. Nonetheless, increasing mDTA-1 treatment to 30 mg/kg in ADA-positive mice restores mDTA-1 exposure and GITR engagement on circulating CD3

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Section: Resultssupporting

confidence: 65%

The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice

Brunn

Mauze

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…Our observations which show that Fc receplor-dependent uptake by the tiver is abotished after encapsutaling ctodronate with MLV or SUV contrast with data presented previously by others. It has tseen suggested that hepatic endothctiat cetts can bind sotuble aggregated IgG via Fc-y receptors once Kupflcr cell depiction has been induced by liposomal ctodronate [20]. We have no exptanation for this discrepancy, except lo suggest that ditTercni mechansims may exist for the uptake of smatl soluble immune complexes and the targer cetts which have hcen sensitized by immunogtobutin.…”

Section: Discussionmentioning

confidence: 80%

The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat

Camilleri

Williams

Amos

et al. 1995

Clinical and Experimental Immunology

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SUMMARYClodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlalion between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced ^ 90% inhibition of uptake and clearance of Fc-and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptormediated uptake of these erythroctyes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronale in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.

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“…There is evidence that soluble aggregates, generated by heat or other means, bear many similarities to this type of immune complex including capability to activate immune cells 8,11,14,40 and clearance via the reticuloendothelial system. [41][42][43][44] The size distribution of the immune complex of mAb2 exhibited a dependence on the Figure 7, except that the experimental curves (think lines) were fitted to a "two state" model (see text) provided in Biaevaluation. The thick grey curves are experimental data, and the thin black lines are fitted curves.…”

Section: Discussionmentioning

confidence: 99%

Dimers and multimers of monoclonal IgG1 exhibit higher in vitro binding affinities to Fcγ receptors

Luo

Raso

et al. 2009

mAbs

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Kupffer cell depletionin vivoresults in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells

Abstract: SUMMARYIn the present study we

Cited by 38 publications

References 22 publications

The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice

The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice

The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat

Dimers and multimers of monoclonal IgG1 exhibit higher in vitro binding affinities to Fcγ receptors

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