Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration

Maria Gendelman, Nadine Halligan, Richard Komorowski, Brent Logan, William J Murphy, Bruce R. Blazar, Kirkwood A. Pritchard, William R. Drobyski

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Administration of agonistic monoclonal antibodies or recombinant cytokines is a potential approach to enhance antitumor immunity in bone marrow (BM) transplant recipients, but is complicated by toxicity due to proinflammatory cytokine-mediated vital organ damage. We used a murine syngeneic bone marrow transplant (BMT) model, in which administration of anti-CD40 antibody early after BMT results in overproduction of interleukin-12 (IL-12) and interferon-γ (IFN-γ), and lethal gut toxicity to examine the protective effect of the spin trap inhibitor, alpha phenyl-tert-butyl nitrone (PBN). Administration of PBN protected transplant recipients from mortality by significantly attenuating gut toxicity, but did not effect a reduction in the levels of proinflammatory cytokines (IL-12, IFN-γ, tumor necrosis factor α [TNF-α], or nitrate/nitrite). Moreover, PBN did not compromise anti-CD40 antibody-mediated antitumor effects in a nontransplantation lymphoma model. Collectively, these data suggest that PBN administration may represent a novel approach for reduction of toxicity without compromise of antitumor effects resulting from administration of therapeutic antibodies in both transplantation and nontransplantation settings.

Original languageEnglish (US)
Pages (from-to)428-431
Number of pages4
JournalBlood
Volume105
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Transplants
Bone Marrow
Toxicity
Cytokines
Antibodies
Interleukin-12
Bone
Interferons
Anti-Idiotypic Antibodies
Nitrites
Nitrates
Immunity
Lymphoma
Tumor Necrosis Factor-alpha
Transplantation
Monoclonal Antibodies
Mortality
phenyl-N-tert-butylnitrone
Transplant Recipients
nitrones

ASJC Scopus subject areas

  • Hematology

Cite this

Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration. / Gendelman, Maria; Halligan, Nadine; Komorowski, Richard; Logan, Brent; Murphy, William J; Blazar, Bruce R.; Pritchard, Kirkwood A.; Drobyski, William R.

In: Blood, Vol. 105, No. 1, 01.01.2005, p. 428-431.

Research output: Contribution to journalArticle

Gendelman, Maria ; Halligan, Nadine ; Komorowski, Richard ; Logan, Brent ; Murphy, William J ; Blazar, Bruce R. ; Pritchard, Kirkwood A. ; Drobyski, William R. / Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration. In: Blood. 2005 ; Vol. 105, No. 1. pp. 428-431.
@article{1d662baae2d9441fb91bbdd799539010,
title = "Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration",
abstract = "Administration of agonistic monoclonal antibodies or recombinant cytokines is a potential approach to enhance antitumor immunity in bone marrow (BM) transplant recipients, but is complicated by toxicity due to proinflammatory cytokine-mediated vital organ damage. We used a murine syngeneic bone marrow transplant (BMT) model, in which administration of anti-CD40 antibody early after BMT results in overproduction of interleukin-12 (IL-12) and interferon-γ (IFN-γ), and lethal gut toxicity to examine the protective effect of the spin trap inhibitor, alpha phenyl-tert-butyl nitrone (PBN). Administration of PBN protected transplant recipients from mortality by significantly attenuating gut toxicity, but did not effect a reduction in the levels of proinflammatory cytokines (IL-12, IFN-γ, tumor necrosis factor α [TNF-α], or nitrate/nitrite). Moreover, PBN did not compromise anti-CD40 antibody-mediated antitumor effects in a nontransplantation lymphoma model. Collectively, these data suggest that PBN administration may represent a novel approach for reduction of toxicity without compromise of antitumor effects resulting from administration of therapeutic antibodies in both transplantation and nontransplantation settings.",
author = "Maria Gendelman and Nadine Halligan and Richard Komorowski and Brent Logan and Murphy, {William J} and Blazar, {Bruce R.} and Pritchard, {Kirkwood A.} and Drobyski, {William R.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1182/blood-2004-01-0371",
language = "English (US)",
volume = "105",
pages = "428--431",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration

AU - Gendelman, Maria

AU - Halligan, Nadine

AU - Komorowski, Richard

AU - Logan, Brent

AU - Murphy, William J

AU - Blazar, Bruce R.

AU - Pritchard, Kirkwood A.

AU - Drobyski, William R.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Administration of agonistic monoclonal antibodies or recombinant cytokines is a potential approach to enhance antitumor immunity in bone marrow (BM) transplant recipients, but is complicated by toxicity due to proinflammatory cytokine-mediated vital organ damage. We used a murine syngeneic bone marrow transplant (BMT) model, in which administration of anti-CD40 antibody early after BMT results in overproduction of interleukin-12 (IL-12) and interferon-γ (IFN-γ), and lethal gut toxicity to examine the protective effect of the spin trap inhibitor, alpha phenyl-tert-butyl nitrone (PBN). Administration of PBN protected transplant recipients from mortality by significantly attenuating gut toxicity, but did not effect a reduction in the levels of proinflammatory cytokines (IL-12, IFN-γ, tumor necrosis factor α [TNF-α], or nitrate/nitrite). Moreover, PBN did not compromise anti-CD40 antibody-mediated antitumor effects in a nontransplantation lymphoma model. Collectively, these data suggest that PBN administration may represent a novel approach for reduction of toxicity without compromise of antitumor effects resulting from administration of therapeutic antibodies in both transplantation and nontransplantation settings.

AB - Administration of agonistic monoclonal antibodies or recombinant cytokines is a potential approach to enhance antitumor immunity in bone marrow (BM) transplant recipients, but is complicated by toxicity due to proinflammatory cytokine-mediated vital organ damage. We used a murine syngeneic bone marrow transplant (BMT) model, in which administration of anti-CD40 antibody early after BMT results in overproduction of interleukin-12 (IL-12) and interferon-γ (IFN-γ), and lethal gut toxicity to examine the protective effect of the spin trap inhibitor, alpha phenyl-tert-butyl nitrone (PBN). Administration of PBN protected transplant recipients from mortality by significantly attenuating gut toxicity, but did not effect a reduction in the levels of proinflammatory cytokines (IL-12, IFN-γ, tumor necrosis factor α [TNF-α], or nitrate/nitrite). Moreover, PBN did not compromise anti-CD40 antibody-mediated antitumor effects in a nontransplantation lymphoma model. Collectively, these data suggest that PBN administration may represent a novel approach for reduction of toxicity without compromise of antitumor effects resulting from administration of therapeutic antibodies in both transplantation and nontransplantation settings.

UR - http://www.scopus.com/inward/record.url?scp=11144225851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144225851&partnerID=8YFLogxK

U2 - 10.1182/blood-2004-01-0371

DO - 10.1182/blood-2004-01-0371

M3 - Article

C2 - 15331451

AN - SCOPUS:11144225851

VL - 105

SP - 428

EP - 431

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -