Control of cancer progression by extracorporeal removal of soluble TNF-alpha receptors

• Published in: Journal of clinical oncology Vol. 38; no. 5_suppl; p. 20
• Main Authors: Josephs, Steven, Segal, Robert, Panahi, Marilyn, Ong, Matthew, Kunkel, Mark, Jafri, Amir, Foster, Jonathan D., Ogilvie, Gregory K.
• Format: Journal Article
• Language: English
• Published: 10.02.2020
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2020.38.5_suppl.20

Abstract only 20 Background: Tumor necrosis factor (TNF)-alpha is a potent antineoplastic cytokine which exerts tumor destruction in part through vascular disruption. Local administration of TNF-alpha exerts profound anti-cancer effects as observed in studies using isolated limb perfusion. However, systemic administration of this cytokine is associated with vascular leakage and limits clinical use. Methods: One method of stimulating localized effects of TNF-alpha is through removal of its soluble receptors, sTNF-R1 and sTNF-R2 using extracorporeal apheresis; ie, Immunopheresis. In this comparative oncology study, we utilized the proprietary LW-02 device to remove sTNF-Rs in pet dogs with varying types of solid malignancies (Part A; n = 12) or with oral malignant melanoma (Part B; n = 8). Canine patients received between 12-24 apheresis treatments over the course of 4 to 8 weeks. Results: In the over 300 immunopheresis treatments, no device associated adverse effects were reported. Consistent reduction of sTNF-Rs was observed, as measured by decreased plasma levels during treatment as well as elution of sTNF-Rs from the cartridge. Of 17 evaluable dogs who completed treatment, 7 had disease stabilization or regression as confirmed by cRECIST criteria. Conclusions: These data strongly support the clinical translation of the LW-02 device as a potential therapeutic approach for treating solid malignancies/melanoma, either as mono- or as adjuvant therapy.