Selective removal of proteins and microvesicles ex vivo from blood of pancreatic cancer patients using bioengineered adsorption filters

Abstract

Metastatic pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with limited efficacious therapeutic options. Recent investigations have provided proof of concept that circulating tumor cells (CTCs) are reduced by purification of PDAC patient blood samples through ExThera Seraph100™ adsorption filters. Whether additional tumorigenic factors are also removed remains inadequately studied. Here, matched whole blood and purified blood samples from seven PDAC patients were analyzed for microparticle and soluble protein content. For microparticle analysis, patient samples were stratified by abundance. Filters markedly reduced ∼200-nm particles when in high abundance. Exosomes, or vesicles ranging from ∼50 to 150-nm were not significantly affected by the purification process. Proteomic analysis of plasma from the whole and purified blood revealed only a limited number of differentially expressed proteins. The complement C1Q proteins were reduced by the purification process, likely due to their heparin binding affinity. In contrast, there was an elevation in cytoplasmic proteins after purification, which may be due to cell destruction. Taken together, this study shows the selective removal of a subfraction of larger (>200 nm) microvesicles and C1Q during blood purification by the Seraph100™. The clinical significance of these findings requires further study.