Selective removal of soluble tumor necrosis factor receptors by apheresis as a novel immunotherapy approach for triple-negative breast cancer.

Abstract

e13065 Background: Although the activity of the cytokine TNF-α against diverse tumor types has been widely documented, safe and effective therapies for augmenting this pathway are lacking. An immunoadsorption device, the LW-02 Column, has been developed as a subtractive immunotherapy approach to remove soluble TNF-α receptors (sTNF-R1 and sTNF-R2) from cancer patients’ plasma using apheresis. Since soluble TNF-α receptors bind to and neutralize the activity of TNF-α, their depletion from plasma is performed to unleash the anti-tumor effects of endogenous TNF-α. The LW-02 Column contains an inert matrix to which a recombinant TNF-α polypeptide (single-chain TNF-α; scTNF) is covalently coupled as a ligand for capturing sTNF-R1 and sTNF-R2. This study evaluated key performance features of the LW-02 Column when used as a monotherapy or with chemotherapy in patients with advanced TNBC [ClinicalTrials.gov Identifier: NCT04004910]. Methods: As part of the ongoing clinical study, 28 patients with advanced TNBC underwent 862 LW-02 Column Immunopheresis procedures at 3 sites (mean=22.5; range=2–109) using the Spectra Optia Apheresis System (Terumo BCT, Inc.); 10 patients received LW-02 Column monotherapy and 18 received LW-02 Column therapy with various chemotherapy regimens. Therapy with the LW-02 Column was performed 3x/week for at least 16 weeks by processing 2 plasma volumes per treatment. Adverse events and tolerability of the therapy were monitored. Assessments were performed to determine the LW-02 Column’s target specificity and capture efficiency. The amount of scTNF ligand that could leach from the column during the procedures was also measured. Results: No serious device-related adverse events have been reported in this study. After 30 minutes of apheresis using the LW-02 Column, the mean capture efficiencies for sTNF-R1 and sTNF-R2 from TNBC patients’ plasma were 95.2% and 79.6%, respectively. The LW-02 Column was highly selective for removing sTNF-R1 and sTNR-R2 from total plasma proteins. The mean total amount of scTNF that may leach from the LW-02 Column (109 ng per apheresis session) is orders of magnitude lower than TNF-α concentrations that are known to trigger clinically meaningful effects. Conclusions: In patients with advanced TNBC, subtractive immunotherapy with the LW-02 Column either as a monotherapy or with chemotherapy is safe and achieves effective depletion of soluble TNF-α receptors from plasma. Evaluation of the safety and efficacy of the LW-02 Column is ongoing in TNBC patients as well as in studies of other solid tumor types. The LW-02 Column provides a novel and promising immunotherapy approach for augmenting the anti-cancer activity of the TNF-α pathway. Clinical trial information: NCT04004910.