TY - JOUR
T1 - Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening
AU - Gasparetto, Maura
AU - Gentry, Tracy
AU - Sebti, Said
AU - O'Bryan, Erica
AU - Nimmanapalli, Ramadevi
AU - Blaskovich, Michelle A.
AU - Bhalla, Kapil
AU - Rizzieri, David
AU - Haaland, Perry
AU - Dunne, Jack
AU - Smith, Clay
N1 - Funding Information:
This work was supported by grant NIH RO1 #NIH RO-1 HL65255-01. M.G. was also supported by a grant from Istituto Pasteur-Fondazione Cenci Bolognetti.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - ADCC
KW - antibody-dependant cellular cytotoxicity
KW - CDCC
KW - complement-dependant cellular cytotoxicity
KW - FC-HCS
KW - flow cytometric high-content screening
KW - Flow cytometry
KW - High content screening
KW - National Cancer Institute
KW - NCI
KW - PI
KW - propidium iodide
KW - Rituximab
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U2 - 10.1016/j.jim.2004.06.003
DO - 10.1016/j.jim.2004.06.003
M3 - Article
C2 - 15350512
AN - SCOPUS:4444343792
VL - 292
SP - 59
EP - 71
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
SN - 0022-1759
IS - 1-2
ER -