Shipra Gandhi, Mateusz Opyrchal, Melissa J Grimm, Ronald T Slomba, Kathleen M Kokolus, Agnieszka Witkiewicz, Kristopher Attwood, Adrienne Groman, Lauren Williams, Mary Lynne Tarquini, Paul K Wallace, Kah Teong Soh, Hans Minderman, Orla Maguire, Tracey L O'Connor, Amy P Early, Ellis G Levine, Pawel Kalinski
BACKGROUND: Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs. METHODS: Six evaluable patients (33-69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m2 ; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks...
November 2023: Journal for Immunotherapy of Cancer