Death receptor 5 agonistic antibody PRO95780: preclinical pharmacokinetics and concentration–effect relationship support clinical dose and regimen selection

Xiang, Hong; Reyes, Arthur E.; Eppler, Steve; Kelley, Sean K.; Damico‐Beyer, Lisa A.

doi:10.1007/s00280-013-2200-3

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…1), with 7 antibodies having a clearance rate greater than 20 mL/day/kg, a value determined by analysis of receiver operating characteristic (ROC) curves and other considerations (see below) These reported clearance values fall within the expected range for IgG1 clearance rates in mice. [14][15][16] The full set of PK curves is displayed in Figure S1.…”

Section: Measurement Of Clearance Rates In Mice For a Panel Of Human mentioning

confidence: 99%

High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

Kelly

Sun

Jain

et al. 2015

mAbs

114

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(2015) High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice, mAbs, 7:4, 770-777, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Keywords: high throughput screening, developability, monoclonal antibody, PK, clearance, cross-interaction, self-interaction, non-specificity, stickinessAbbreviations: mAb, monoclonal antibody; PSR, poly specificity reagent; SMP, soluble membrane proteins; CSI-BLI, clone self-interaction-biolayer interferometry; CIC, cross-interaction chromatography; SEC, size exclusion chromatography; AC-SINS, affinity capture self-interaction nanoparticle spectroscopy; SEC, size exclusion chromatographyAlthough improvements in technology for the isolation of potential therapeutic antibodies have made the process increasingly predictable, the development of biologically active monoclonal antibodies (mAbs) into drugs can often be impeded by developability issues such as poor expression, solubility, and promiscuous cross-reactivity. Establishing early stage developability screening assays capable of predicting late stage behavior is therefore of high value to minimize development risks. Toward this goal, we selected a panel of 16 monoclonal antibodies (mAbs) representing different developability profiles, in terms of self-and cross-interaction propensity, and examined their downstream behavior from expression titer to accelerated stability and pharmacokinetics in mice. Clearance rates showed significant rank-order correlations to 2 cross-interaction related assays, with the closest correlation to a non-specificity assay on the surface of yeast. Additionally, 2 self-association assays correlated with each other but not to mouse clearance rate. This case study suggests that combining assays capable of high throughput screening of self-and cross-interaction early in the discovery stage could significantly lower downstream development risks.

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Section: Measurement Of Clearance Rates In Mice For a Panel Of Human mentioning

confidence: 99%

High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

Kelly

Sun

Jain

et al. 2015

mAbs

114

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“…This approach assumes a comparable exposure–anti-tumor activity relationship between the humans and xenograft mouse model. A similar tumor-growth-inhibition-model-based approach has been reported for PRO95780 (anti-DR5 antibody) [ 70 ], rhuMAb VEGF (anti-VEGF antibody) [ 71 ], SI-B001 (anti-EGFR/HER3 bispecific antibody) [ 67 ], and MCLA-128 (anti-HER2/HER3 bispecific antibody). Since the mechanistic process is not incorporated into this model, it cannot account for the mechanism-based inter-species differences in effective concentration.…”

Section: Traditional Model-based Prediction Of Human Pkpdmentioning

confidence: 82%

Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation

Haraya¹,

Tsutsui²,

Komori³

et al. 2022

Pharmaceuticals

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Therapeutic monoclonal antibodies (mAbs) have been a promising therapeutic approach for several diseases and a wide variety of mAbs are being evaluated in clinical trials. To accelerate clinical development and improve the probability of success, pharmacokinetics and pharmacodynamics (PKPD) in humans must be predicted before clinical trials can begin. Traditionally, empirical-approach-based PKPD prediction has been applied for a long time. Recently, modeling and simulation (M&S) methods have also become valuable for quantitatively predicting PKPD in humans. Although several models (e.g., the compartment model, Michaelis–Menten model, target-mediated drug disposition model, and physiologically based pharmacokinetic model) have been established and used to predict the PKPD of mAbs in humans, more complex mechanistic models, such as the quantitative systemics pharmacology model, have been recently developed. This review summarizes the recent advances and future direction of M&S-based approaches to the quantitative prediction of human PKPD for mAbs.

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“…TRAIL-mimicking antibody, which bounds to receptor and activated it, can be a good substitute therapy. Today, the scientists were presented number of antibodies against DR4 and DR5 for treatment of different kinds of malignancies which are in clinical trials [27][28][29][30][31]. Although unfortunately, almost all of them, such TRA-8, WD1 and … could not kill cancerous cells lonely and need the association of chemotraphical treatments [32,33].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of three kinds of IgYs, (normal, nanoliposomal and nanoparticle conjugated), which are produced against the small domains of DR5 protein on cancer cells

Amirijavid

Entezari

2018

IET nanobiotechnol.

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Cancer treatment with several kinds of drugs, especially targets the apoptotic pathways nowadays. TNF-related apoptosis-inducing ligand (TRAIL) as one of the important members of death receptors, significantly trigger induction of apoptosis in cancer cells. Three conserved domains of Death receptor (DR5) protein extracellular domain, which are fortified cysteine, were chosen and chemically synthesised. Hens were immunised with nano-liposomal peptides, and as a result the purified Immunoglobulin (IgYs) remarkably killed the cancerous MCF7 cells. The flow cytometric assay, confirmed the apoptotic death. Among several kinds of carriers that were used in this research, the nano-liposomal and nanoparticle conjugated, both were acceptable choices for drug delivery. Furthermore, the IgY against DR5's small peptides with such carriers successfully reached the target and significantly killed the cancer cells via apoptosis.

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Death receptor 5 agonistic antibody PRO95780: preclinical pharmacokinetics and concentration–effect relationship support clinical dose and regimen selection

Abstract: PRO95780 has linear PK in mice, rats, and monkeys. Estimated TSCs varied among different xenograft models. A projected target dose in humans is achievable for Q2W administration within the dose range used for other commercial mAbs.

Cited by 8 publications

References 32 publications

High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation

Comparison of the effects of three kinds of IgYs, (normal, nanoliposomal and nanoparticle conjugated), which are produced against the small domains of DR5 protein on cancer cells

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