Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody

Bert A 't Hart, Herbert P M Brok, Ed Remarque, Jacqueline Benson, George Treacy, Sandra Amor, Rogier Q Hintzen, Jon D Laman, Jan Bauer, Erwin L A Blezer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.

Original languageEnglish
Pages (from-to)4761-8
Number of pages8
JournalJournal of Immunology
Volume175
Issue number7
Publication statusPublished - 1 Oct 2005

Cite this

't Hart, B. A., Brok, H. P. M., Remarque, E., Benson, J., Treacy, G., Amor, S., ... Blezer, E. L. A. (2005). Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody. Journal of Immunology, 175(7), 4761-8.
't Hart, Bert A ; Brok, Herbert P M ; Remarque, Ed ; Benson, Jacqueline ; Treacy, George ; Amor, Sandra ; Hintzen, Rogier Q ; Laman, Jon D ; Bauer, Jan ; Blezer, Erwin L A. / Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody. In: Journal of Immunology. 2005 ; Vol. 175, No. 7. pp. 4761-8.
@article{d29d2f14bb3f49f09d1da2ad507d5561,
title = "Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody",
abstract = "IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.",
keywords = "Animals, Antibodies, Monoclonal, Brain, Callithrix, Disease Models, Animal, Disease Progression, Drug Evaluation, Preclinical, Encephalomyelitis, Autoimmune, Experimental, Humans, Interleukin-12, Interleukin-12 Subunit p40, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Protein Subunits, Journal Article",
author = "{'t Hart}, {Bert A} and Brok, {Herbert P M} and Ed Remarque and Jacqueline Benson and George Treacy and Sandra Amor and Hintzen, {Rogier Q} and Laman, {Jon D} and Jan Bauer and Blezer, {Erwin L A}",
year = "2005",
month = "10",
day = "1",
language = "English",
volume = "175",
pages = "4761--8",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

't Hart, BA, Brok, HPM, Remarque, E, Benson, J, Treacy, G, Amor, S, Hintzen, RQ, Laman, JD, Bauer, J & Blezer, ELA 2005, 'Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody' Journal of Immunology, vol. 175, no. 7, pp. 4761-8.

Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody. / 't Hart, Bert A; Brok, Herbert P M; Remarque, Ed; Benson, Jacqueline; Treacy, George; Amor, Sandra; Hintzen, Rogier Q; Laman, Jon D; Bauer, Jan; Blezer, Erwin L A.

In: Journal of Immunology, Vol. 175, No. 7, 01.10.2005, p. 4761-8.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody

AU - 't Hart, Bert A

AU - Brok, Herbert P M

AU - Remarque, Ed

AU - Benson, Jacqueline

AU - Treacy, George

AU - Amor, Sandra

AU - Hintzen, Rogier Q

AU - Laman, Jon D

AU - Bauer, Jan

AU - Blezer, Erwin L A

PY - 2005/10/1

Y1 - 2005/10/1

N2 - IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.

AB - IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.

KW - Animals

KW - Antibodies, Monoclonal

KW - Brain

KW - Callithrix

KW - Disease Models, Animal

KW - Disease Progression

KW - Drug Evaluation, Preclinical

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Humans

KW - Interleukin-12

KW - Interleukin-12 Subunit p40

KW - Magnetic Resonance Imaging

KW - Male

KW - Multiple Sclerosis

KW - Protein Subunits

KW - Journal Article

M3 - Article

VL - 175

SP - 4761

EP - 4768

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -