Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening

Maura Gasparetto, Tracy Gentry, Said Sebti, Erica O'Bryan, Ramadevi Nimmanapalli, Michelle A. Blaskovich, Kapil Bhalla, David Rizzieri, Perry Haaland, Jack Dunne, Clay Smith

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

In this report, we describe a new flow cytometry technique termed flow cytometric high-content screening (FC-HCS) which involves semi-automated processing and analysis of multiparameter flow cytometry samples. As a first test of the FC-HCS technique, we used it to screen a 2000-compound library, called the National Cancer Institute (NCI) Diversity Set, to identify agents that would enhance the anti-lymphoma activity of the therapeutic monoclonal antibody rituximab. FC-HCS identified 15 compounds from the Diversity Set that significantly enhanced the ability of rituximab to inhibit cell cycle progression and induce apoptosis in lymphoma cells. The validity of the screening results was confirmed for several compounds using additional assays of cell proliferation, apoptosis and cell growth. The FC-HCS technique was relatively simple and reliable and could process up to 1000 samples/day on a single flow cytometer. The FC-HCS technique may be useful for a variety of applications including drug discovery, immunologic monitoring of patients, functional genomics studies and tissue engineering efforts.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalJournal of Immunological Methods
Volume292
Issue number1-2
DOIs
StatePublished - Sep 2004

Keywords

  • ADCC
  • antibody-dependant cellular cytotoxicity
  • CDCC
  • complement-dependant cellular cytotoxicity
  • FC-HCS
  • flow cytometric high-content screening
  • Flow cytometry
  • High content screening
  • National Cancer Institute
  • NCI
  • PI
  • propidium iodide
  • Rituximab

ASJC Scopus subject areas

  • Biotechnology
  • Immunology

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