Gl.EXO · Innovative tools to detect Glioblastoma (GBM) exosomes

Innovative tools to detect Glioblastoma (GBM) exosomes

Glioblastoma is the most frequent and aggressive primary brain tumour in adults (Louis et al., 2016; Sant et al., 2012). Despite advances in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal, with a median survival of 14–15 months (Urbanska et al., 2014). A small population of cancer stem cells (glioblastoma stem cells, GSCs) that retains stem cell properties, including self-renewal and multipotency, are deemed responsible for the frequent relapse of GBM and its resistance to conventional therapeutics (Bao, S. et al. 2006; Bovenberg, M.S. 2013). Despite the important advancements in the treatment of GBM the clinical outcome of patients is still disappointing. Moreover, the traditional diagnostic methods are limited by the tumour tissue accessibility. Therefore, the research of circulating biomarkers is a fundamental challenge that can allow detecting tumours early, when they are most treatable, consequently improving disease outcome and health costs. Indeed, A40s-based assay could be crucial for an easily and early-stage diagnosis of GBM along with a quick and always available tool for monitoring GBM treatments and possible tumour relapse. This will give a better treatment of patients with great impact both on patients’ overall survivor and quality of life and on health systems economics. Gl.EXO made important advances in pursuing 3 objectives: The first objective was to characterize A40s aptamer binding on blood exosomal samples. Indeed, exosome-coated plates have been generated and used with aptmer-based reporter system to convert target binding into a detectable signal. Different protocols have been tested with the aim of selectively discriminating positive to negative exosomes from serum and the possibility to increase assay sensitivity through an additional different aptamer. The second objective was to evaluate the clinical potential of A40s by analysing its ability to bind tumoral exosomes from human serum. Indeed, A40s has been tested on a bigger cohort of patients with different methods. Our goal was to demonstrate that A40s is able to be translatable into the clinical practice for detecting GBM exosomes in the blood of GBM patients. The third objective was the theragnostic application of A40s and so its use as a therapeutic tool. Here, our aim was to exploit the aptamer exosomal binding properties together with its ability to inhibit exosomes functional effects. A40s has been able to affect exosomal pro-tumorigenic effects. Additionally, A40s has been proven to be able to deliver near-infrared agents usable for both imaging and photodynamic therapy, demonstrating A40s possible use as theragnostic.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз