Abstract PL04-02: Extracellular vesicles as opportunities for integrative or focused liquid biopsy studies

Abstract

Abstract Background: For patients who present with or develop progressive, metastatic cancer, new immunotherapies offer significant hope of remission or cure. However, many of the most effective immunotherapies and cancer vaccines are often effective in fewer than 50% of patients treated, and assessment of treatment responses is only feasible after multiple weeks or months of treatment, a period of time during which other more effective treatment options or combinations might have been selected instead for the non-responding patients. Therefore, improved methods for monitoring treatment responses, especially early during treatment, are needed. Extracellular Vesicles (EVs), are continuously released and carry surface receptors and RNA/DNA cargo related to the state of their cell of origin. Thus, EVs may enable near-real-time clinical blood and/or urine tests for early screening, risk stratification, and monitoring of cancer immunotherapies. Methods: To extract the information that is carried by EVs, our lab has developed a first-in-class pipeline to characterize EV heterogeneity and provide high-sensitivity quantification of informative EV subsets by combining multiplex assays with high-resolution, single EV flow cytometric methods together into a Multiplex-to-Single EV Analysis (Mt-SEA) pipeline. Results: In preliminary data from ongoing clinical trials, we have identified EV subset changes that correspond to responses to treatment. Moreover, as with other complex biological systems, we find that it is possible to interrogate several dimensions of EV cargo to further improve the utility and impact of this approach. The methods and tools that we have developed are being made available for use in the wider research community. Conclusions: We hypothesize that identification of sensitive and specific EV-associated biomarkers for responses to immunotherapies would significantly advance efforts to improve treatment outcomes and quality of life for advanced cancer patients. The Mt-SEA Pipeline of methods developed by the NCI Translational Nanobiology lab establishes a foundation for interrogating different genetic and molecular profiles in tumor-derived and immune cell-derived EVs in urine and/or blood within 1-2 weeks of the start of treatment. Citation Format: Joshua Welsh, Kenneth Aldape, Jennifer Jones. Extracellular vesicles as opportunities for integrative or focused liquid biopsy studies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr PL04-02. doi:10.1158/1535-7163.TARG-19-PL04-02