Abstract 4816: Development of an integrated analysis platform of circulating melanoma cells for PD-L1 expression as a predictive biomarker

Novel therapies that target the PD-1/PD-L1 axis have shown great potential to improve survival for patients with advanced melanoma. However, there are limited predictive biomarkers to identify patients who may respond to this class of agents. Previous studies suggest that a subset of responders to PD-1/PD-L1 targeting therapies have expression of PD-L1 in tumor biopsies. The development of these predictive biomarkers is complicated by intratumoral heterogeneity across primary and metastatic lesions for PD-L1 expression. Circulating tumor cells (CTCs) are one potential source of tumor samples for serial analysis. An integrated CTC capture and analysis technology known as the VERSA (Versatile Exclusion-based Rare Sample Analysis) platform permits evaluation of CTCs at the protein, DNA and mRNA level for biomarkers of both therapeutic response and resistance. Using this platform, we have developed a method to isolate circulating tumor cells from patients with advanced melanoma. Using a cocktail of capture monoclonal antibodies including targets of CD146, GD2 and NG2, we have recovered cells across multiple cell lines with high efficiency. Using single antibody capture of SK-Mel-28 cells, capture was 52%, 54%, and 45% with CD146, GD2 and NG2 targets respectively. However, when using a cocktail of capture antibodies containing CD146, GD2 and NG2, capture increased to 92%. Similar results were obtained with other melanoma cell lines including, 624 and M21 cell lines. Cells were also stained for PD-L1 as a potential predictive biomarker of response to PD-L1 and PD-1 targeting immunotherapies. We are now collecting patient samples with this capture platform to identify CTCs expressing PD-L1 as a potential predictive biomarker to PD-1/PD-L1 targeting therapies. Citation Format: Benjamin K. Gibbs, Lindsay N. Strotman, Stephanie M. Thiede, Jamie M. Sperger, Benjamin P. Casavant, Scott M. Berry, David J. Beebe, Joshua M. Lang. Development of an integrated analysis platform of circulating melanoma cells for PD-L1 expression as a predictive biomarker. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4816. doi:10.1158/1538-7445.AM2014-4816