Effect of tumor necrosis factor alpha on biodistribution of an anti-epidermal growth factor receptor (EGFr) monoclonal antibody in vivo

J. L. Murray, C. Wilmanns, R. Kilbourn, K. Mujoo, L. P. Kasi, H. Z. Zhang, N. Donato, M. G. Rosenblum

Research output: Contribution to journalArticle

Abstract

In a previous study we demonstrated that tumor necrosis factor alpha (TNFα) was capable of increasing binding of an anti-epidermal growth factor receptor monoclonal antibody (Mab), A108, to melanoma cells in vitro through regulation of the EGFr receptor. To determine whether similar effects occurred in vivo, nude mice bearing subcutaneous and visceral human tumor xenografts of melanoma cell line DX3 were given TNFα (103, 104 or 105 U/day x 6 days) or normal saline (control) followed by intravenous injections of 125I-labeled A108, along with control Mab, 131I-NR2AD. Twenty-four hours later mice were sacrificed and the percent injected dose of each Mab determined in tumors and normal organs. TNFα caused a 1 to 2-fold increase in tumor targeting of both Mabs over controls (p < 0.05). Increased blood and heart uptake of both Mabs was also observed. The increase in normal tissues was significantly blocked by the administration of N(G)-methyl-L-arginine, a selective inhibitor of nitric oxide synthesis. Examination of excised tumors for EGFr expression in TNFα treated versus saline treated mice revealed that specific upregulation of EGFr occurred only in liver tumors. These data suggest that TNFα acts to enhance targeting of Mabs through both enhancement of EGFr on tumors as well as by selective vascular endothelial cell damage...and that these changes vary with respect to tumor location.

Original languageEnglish (US)
Pages (from-to)261-275
Number of pages15
JournalAntibody, Immunoconjugates, and Radiopharmaceuticals
Volume7
Issue number4
StatePublished - 1994

ASJC Scopus subject areas

  • Immunology
  • Radiology Nuclear Medicine and imaging

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