Enhanced delivery improves the efficacy of a tumor-specific doxorubicin immunoconjugate in a human brain tumor xenograft model

Laura G. Remsen, Pamela A. Trail, Ingegerd Hellström, Karl Erik Hellström, Edward Neuwelt

43 Scopus citations

Abstract

OBJECTIVE: To evaluate dose intensification with osmotic blood-brain barrier disruption (BBBD) and the potential use of drug targeting with monoclonal antibody (MAb) BR96 conjugated to doxorubicin (BR96-DOX, now called SGN15) for treatment of intracerebral and subcutaneous human LX-1 small cell lung carcinoma xenografts in rats. METHODS: LX-1 tumors with high, low, or heterogeneous levels of the Lewis(y) antigen for BR96 were evaluated. Rats were treated with intracarotid or intravenous BR96-DOX, with or without osmotic BBBD. RESULTS: Both BR96-DOX and MAb BR96 treatment resulted in significant regression of subcutaneous tumors, in contrast to control groups including doxorubicin alone, saline, or nonbinding doxorubicin immunoconjugate. BR96-DOX delivered with BBBD to brain tumors with low antigen expression resulted in significantly (P

Original languageEnglish (US)
Pages (from-to)704-709
Number of pages6
JournalNeurosurgery
Volume46
Issue number3
Publication statusPublished - Mar 2000

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Keywords

  • Brain tumor
  • Doxombicin
  • Immunoconjugate
  • Targeted therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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