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Development of a circulating tumor cell assay for use in selecting patients for a novel antibody-drug conjugate therapy*.

2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2015.33.15_suppl.e22022

1527-7755

Xiaolei Qiu, Hilda Beas, Madeleine Matias, Monalisa Ray, Sunil Pandit, Harwinder Sidhu, Albert J. Chmura, Rong Jiang, Sebastian Kronmueller, J Atherton Philip, Karen Marfurt, Michael J. Pugia, Omar D. Perez, Steven Pirie‐Shepherd, Arejas J. Uzgiris,

CAR-T cell therapy research

e22022 Background: Antigens that are expressed in various cancers and substantially absent from normal tissue are potential targets for high-affinity antibodies developed for use in targeting cytotoxic agents to treat patients with such antigen-positive cancers. The results of this research are intended to support a technical feasibility recommendation regarding the use of the developed assay in future clinical trials to identify patients with circulating tumor cells (CTC) positively expressing an antibody-drug conjugate (ADC) target. Methods: A rare-cell detection platform* utilized for automated isolation and characterization of CTC was developed by Siemens Healthcare Diagnostics Innovations (Elkhart, IN). The Siemens Clinical Laboratory (SCL) (Berkeley, CA) developed a quantitative antigen expression assay* for this platform in collaboration with Pfizer Oncology Research, which provided 25 non-small cell lung carcinoma (NSCLC) samples. Analytical performance data were evaluated with cancer cell lines spiked in normal blood. Clinical samples from cancer patients were drawn in blood collection tubes and shipped to SCL at ambient temperature. Cancer cells were isolated by filtration, stained fluorescently, and scanned microscopically. ADC target signal intensity was analyzed quantitatively for each positive cell. Results: Analytical performance data included greater than 79% recovery from controls ranging from 4 to 200 cancer cells spiked per 8 mL of whole blood. With formalin-fixed cell line controls, recovery was greater than 90%. Twenty-four out of 25 clinical samples were successfully processed, and 62.5% (15 out of 24) were positive for detection of the drug target. Conclusions: Detection of this circulating biomarker in late-stage (III and IV) NSCLC patients was sufficiently frequent that the test could potentially find wider application in the areas of diagnosis and monitoring of lung cancer. *The prototype CTC platform and assay are for research use only. They are not available for sale.