Lyon, Robert P.;
Ryan, Maureen C.;
Sutherland, May;
Meyer, Brad;
Yu, Changpu;
Kostner, Heather;
Miyamoto, Jamie;
Benjamin, Dennis R.
Abstract 4394: Development of parallel conjugation and assay methodologies to screen for antibodies with optimal properties for use as antibody-drug conjugates
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Media type:
E-Article
Title:
Abstract 4394: Development of parallel conjugation and assay methodologies to screen for antibodies with optimal properties for use as antibody-drug conjugates
Contributor:
Lyon, Robert P.;
Ryan, Maureen C.;
Sutherland, May;
Meyer, Brad;
Yu, Changpu;
Kostner, Heather;
Miyamoto, Jamie;
Benjamin, Dennis R.
imprint:
American Association for Cancer Research (AACR), 2010
Description:
<jats:title>Abstract</jats:title>
<jats:p>The activity of antibody-drug conjugates (ADCs) on cancer cells can be affected by a multitude of factors, such as binding affinity, rate of internalization, subcellular trafficking, and efficient drug release within the target cell population. Consequently, the properties of an ideal antibody for drug delivery are not necessarily the same as those for a therapeutic naked antibody. Furthermore, the use of indirect assays involving the use of secondary antibodies to screen for optimal ADCs can be misleading, since crosslinking on the cell surface can lead to altered downstream events, and the affinity of the secondary antibody constrains the dynamic range of the assay. When seeking candidate antibodies directed against a novel antigen for ADC therapy, it is therefore most desirable to screen a large panel in the form of ADCs and evaluate their cytotoxic activities, since these results provide a direct measurement of parameters that can affect cytotoxic activity. However, when dealing with microgram quantities of a large number of antibodies as is typical of an antibody discovery campaign, the yields from conventional conjugation methodologies are limiting. We developed a novel approach that addresses this issue and have successfully applied it to the discovery of optimal ADCs out of a large panel of candidate antibodies. The technology is currently being applied to the discovery of ADCs against antigens of interest for targeted drug delivery.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4394.</jats:p>