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Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration. Blood 2005 Jan 01;105(1):428-31 PMID: 15331451

Pubmed ID

15331451

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-gamma (IFN-gamma), 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-gamma, tumor necrosis factor alpha [TNF-alpha], 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 List

Gendelman M, Halligan N, Komorowski R, Logan B, Murphy WJ, Blazar BR, Pritchard KA Jr, Drobyski WR

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




Scopus

2-s2.0-11144225851   8 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
Antineoplastic Agents
Bone Marrow Transplantation
CD40 Antigens
Cyclic N-Oxides
Cytokines
Lymphoma
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Nitrogen Oxides
Survival Rate
Syndrome
Transplantation
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70