Background: Vascular endothelial-derived growth factor A(VEGFA) has been proven to be integral in the molecular pathogenesis of metastasis and tumor growth. It is known that VEGF is responsible for encoding a heparin-binding protein, which exists as a disulfide-linked homodimer which serves to promote the propagation and movement of vascular endothelial cells. This is essential for both pathological and physiological angiogenesis. CETC and cancer stem cells are potent secretors of VEGFA which is an essential cytokine that facilitates new vascular vessel formation, thus further enabling metastatic tumor growth. Methods: We developed a new extracorporeal microbind affinity blood filter platform technology with active heparane sulfate receptors (onco seraph). Heparin is cleaved into short chains which are permanently covalently bound to ultrahigh molecular weight polyethylene (UHMWPE) surfaces to create a new composition of matter. Liquid biopsy established high capacity for the rapid removal of CETC and PDAC cancer stem cells. Onco seraph was investigated in a dose escalation phase I/II clinical trial in adult patients with advanced and relapsed/refractory solid (what) and/or PDAC after standard of care and other lines of therapy failed in preventing disease progression. Results: To date 12 patients have been treated with onco seraph. No patient experienced treatment related adverse effects. Best responses include complete responses and stable disease at a low oncoseraph dose. Greatest efficacy was observed for patients whose liquid biopsy revealed significant and rapid reduction of CETC and cancer stem cells, followed by greater than 50% reduction in circulating VEGFA. Conclusions: This data supports the conclusion that the onco seraph platform technology is safe and has a high therapeutic value as an extracorporeal treatment for metastatic solid tumors refractory to standard of care.

Citation Format: Sanja ILIC, Vedran Premuzic, Robert Ward. Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A005.