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Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

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Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency. / Saul, Louise; Josephs, Debra H; Cutler, Keith; Bradwell, Andrew; Karagiannis, Panagiotis; Selkirk, Chris; Gould, Hannah J; Jones, Paul; Spicer, James F; Karagiannis, Sophia N.

in: MABS-AUSTIN, Jahrgang 6, Nr. 2, 05.02.2014, S. 509-22.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Saul, L, Josephs, DH, Cutler, K, Bradwell, A, Karagiannis, P, Selkirk, C, Gould, HJ, Jones, P, Spicer, JF & Karagiannis, SN 2014, 'Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency', MABS-AUSTIN, Jg. 6, Nr. 2, S. 509-22. https://doi.org/10.4161/mabs.27828

APA

Saul, L., Josephs, D. H., Cutler, K., Bradwell, A., Karagiannis, P., Selkirk, C., Gould, H. J., Jones, P., Spicer, J. F., & Karagiannis, S. N. (2014). Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency. MABS-AUSTIN, 6(2), 509-22. https://doi.org/10.4161/mabs.27828

Vancouver

Saul L, Josephs DH, Cutler K, Bradwell A, Karagiannis P, Selkirk C et al. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency. MABS-AUSTIN. 2014 Feb 5;6(2):509-22. https://doi.org/10.4161/mabs.27828

Bibtex

@article{d9fe24e0373d46a7abb2d086323698eb,
title = "Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency",
abstract = "BACKGROUND: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.METHODS: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays.RESULTS: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species.CONCLUSION: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies.",
keywords = "Animals, Antibody Affinity, Cells, Cultured, Cytokines/metabolism, Cytotoxicity, Immunologic, Humans, Immunoglobulin E/immunology, Immunotherapy/methods, Lectins, C-Type/metabolism, Leukocytes, Mononuclear/immunology, Macaca fascicularis, Models, Animal, Protein Binding, Receptors, IgE/metabolism, Species Specificity",
author = "Louise Saul and Josephs, {Debra H} and Keith Cutler and Andrew Bradwell and Panagiotis Karagiannis and Chris Selkirk and Gould, {Hannah J} and Paul Jones and Spicer, {James F} and Karagiannis, {Sophia N}",
year = "2014",
month = feb,
day = "5",
doi = "10.4161/mabs.27828",
language = "English",
volume = "6",
pages = "509--22",
journal = "MABS-AUSTIN",
issn = "1942-0862",
publisher = "LANDES BIOSCIENCE",
number = "2",

}

RIS

TY - JOUR

T1 - Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

AU - Saul, Louise

AU - Josephs, Debra H

AU - Cutler, Keith

AU - Bradwell, Andrew

AU - Karagiannis, Panagiotis

AU - Selkirk, Chris

AU - Gould, Hannah J

AU - Jones, Paul

AU - Spicer, James F

AU - Karagiannis, Sophia N

PY - 2014/2/5

Y1 - 2014/2/5

N2 - BACKGROUND: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.METHODS: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays.RESULTS: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species.CONCLUSION: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies.

AB - BACKGROUND: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.METHODS: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays.RESULTS: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species.CONCLUSION: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies.

KW - Animals

KW - Antibody Affinity

KW - Cells, Cultured

KW - Cytokines/metabolism

KW - Cytotoxicity, Immunologic

KW - Humans

KW - Immunoglobulin E/immunology

KW - Immunotherapy/methods

KW - Lectins, C-Type/metabolism

KW - Leukocytes, Mononuclear/immunology

KW - Macaca fascicularis

KW - Models, Animal

KW - Protein Binding

KW - Receptors, IgE/metabolism

KW - Species Specificity

U2 - 10.4161/mabs.27828

DO - 10.4161/mabs.27828

M3 - SCORING: Journal article

C2 - 24492303

VL - 6

SP - 509

EP - 522

JO - MABS-AUSTIN

JF - MABS-AUSTIN

SN - 1942-0862

IS - 2

ER -