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

9 Scopus citations

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

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration'. Together they form a unique fingerprint.

  • Cite this