Saturation monitoring of VX 15/2503, a novel semaphorin 4 D ‐specific antibody, in clinical trials

• Published in: Cytometry. Part B, Clinical cytometry Vol. 90; no. 2; pp. 199 - 208
• Main Authors: Fisher, Terrence L., Seils, Jennifer, Reilly, Christine, Litwin, Virginia, Green, Lisa, Salkowitz‐Bokal, Janelle, Walsh, Robin, Harville, Sarah, Leonard, John E., Smith, Ernest, Zauderer, Maurice
• Format: Journal Article
• Language: English
• Published: 01.03.2016
• ISSN: 1552-4949; 1552-4957
• DOI: 10.1002/cyto.b.21338

Background Receptor occupancy, or saturation, assays are often utilized in preclinical and clinical development programs to evaluate the binding of a biologic to a cellular target. These assays provide critical information regarding the dose of drug required to “saturate” the target as well as important pharmacodymamic (PD) data. A flow cytometric method was developed to measure the degree of Semaphorin 4D (SEMA4D; CD100) saturation by VX15/2303, an investigational monoclonal antibody specific for SEMA4D. Methods The assay detects VX15/2503, a human IgG 4 specific for SEMA4D, with an IgG 4 ‐specific monoclonal antibody. Results Data generated allowed assessment of two related SEMA4D‐specific pharmacodynamic (PD) markers: (1) The measurement of cellular SEMA4D (cSEMA4D) saturation by VX15/2503, and (2) the cell membrane expression levels of cSEMA4D. Conclusions This assay specifically and reproducibly measured cSEMA4D saturation and expression levels. Evaluation of the SEMA4D‐specific PD markers were critical in determining the clinical saturation threshold of cSEMA4D by VX15/2503. © 2015 he Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.