Orr, Brian published the artcilePhase I trial combining chemokine-targeting with loco-regional chemoimmunotherapy for recurrent, platinum-sensitive ovarian cancer shows induction of CXCR3 ligands and markers of type 1 immunity, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Clinical Cancer Research (2022), 28(10), 2038-2049, database is CAplus and MEDLINE.
Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts pos. outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel i.p. chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC. Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with i.p. cisplatin, i.p. rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received i.p. IFNα at 2, 6, and 18 million units (MU), resp. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and i.p. wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, resp. The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 mo, resp. Longitudinal sampling of the peritoneal cavity via i.p. washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 wk. The chemokine-modulating i.p.-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial.
Clinical Cancer Research published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.
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