How validated receptor occupancy flow cytometry assays can impact decisions and support drug development

Cytometry. Part B, Clinical Cytometry
Maxime Moulard, Marie-Laure Ozoux

Abstract

Because of the pressure of significant attrition in drug development, demonstration of target engagement after drug administration enables dose and regimen optimization, patient selection, and stratification from the earliest stages of drug development. The determination of receptor occupancy (RO) can support these efforts. Flow cytometry is one of the preferred technologies to be used based on the important advances in the technology over the last years enabling the simultaneous determination on target cells, of multi intra or surface cell parameters with adequate precision in a regulated environment. Nevertheless, compared to other platforms using the same antigen-antibody binding concept, the flow cytometry approach has faced several challenges, not only due to the technology per se and the diversity of receptor occupancy approaches, but also related to the nature of the matrix where the determination is performed. To illustrate these points, three case studies (antibody-drug conjugate and naked antibody) are provided here to highlight the importance of the choice of the right antibody pair to measure both receptor density (RD) and occupancy by the drug on cancer cells in blood and in bone marrow and the possibility to circu...Continue Reading

References

May 23, 1998·The Biochemical Journal·V BerthelierP Deterre
Aug 10, 2005·Current Opinion in Pharmacology·John M Lambert
Nov 14, 2008·Journal of Pharmacokinetics and Pharmacodynamics·Leonid GibianskyPeiming Ma
May 14, 2009·Journal of the National Cancer Institute·Joel B Finkelstein
Sep 30, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anthony W TolcherIgor Puzanov
Oct 15, 2009·Pharmaceutical Research·Jo CunliffeRuth Coldwell
Jun 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie R BrahmerSuzanne L Topalian
Jul 27, 2010·Journal of Immunological Methods·Cherie L GreenThomas W Mc Closkey
Oct 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefanie DererThomas Valerius
Apr 12, 2013·Cytometry. Part B, Clinical Cytometry·Valeria QuaronaFabio Malavasi
Jun 12, 2013·Frontiers in Bioscience (Landmark Edition)·Andrew J CowanRoland B Walter
Oct 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vincent RibragBertrand Coiffier
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jutta DeckertVéronique Blanc

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Citations

Mar 30, 2016·Cytometry. Part B, Clinical Cytometry·Virginia LitwinJennifer J Stewart
Aug 7, 2018·British Journal of Haematology·Aneel PaulusTaimur Sher
Jan 29, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Gerd Haga BringelandSonia Gavasso
Mar 12, 2021·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Fabian JunkerHenry Kao

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