Recombinant α-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo

James L. Murray, Alexander A. Zukiwski, Kalpana Mujoo, Michael G. Rosenblum

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

To determine whether recombinant human α-interferon (rIFNαA) could enhance tumor uptake of an antimelanoma monoclonal antibody (Mab) 96.5 in vivo, groups of nude mice bearing P97 antigen-positive human melanoma subcutaneous xenografts were given i.m. injections of normal saline or rIFNαA daily for 10 days. On day 7, mice received either 5 μg of 111In-labeled Mab 96.5 or irrelevant 111In-labeled subclass-matched or non-subclass-matched control Mabs. Animals were killed 72 h later and the percent injected dose per gram (%ID/g) in tumor and normal organs was determined. There was a significant (p < 0.001) increase in 96.5 in tumors of IFN-treated mice compared to saline-treated mice and mice receiving irrelevant Mabs. There was also a significantly increased uptake of 96.5 in blood, heart, lung, kidney, and muscle of IFN-treated vs. control mice (p < 0.05). This finding was most likely due to increased antigen shedding since significant differences in %ID/g were not observed between IFN-treated and control mice bearing antigen-negative tumors. Furthermore, P97 content in tumor and tissues of IFN-treated mice bearing melanoma xenografts was significantly higher than in mice without tumors. In summary, IFN enhanced targeting of 96.5 via an antigen-specific mechanism. These data confirm and extend previous studies in other tumor systems, and suggest that clinical trials of Mabs plus IFN might be useful in overcoming poor Mab localization that occurs as a result of antigenic heterogeneity in humans.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalJournal of Biological Response Modifiers
Volume9
Issue number6
StatePublished - Dec 1990

Keywords

  • Antimelanoma monoclonal antibody 96.5
  • Recombinant human α-interferon

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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