Data from Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial

Purpose:Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with IFNs and monocytes.Patients and Methods:Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of IFNs α and γ with monocytes. We translated these preclinical findings into a phase I trial of autologous IFN-activated monocytes administered intraperitoneally to platinum-resistant or -refractory ovarian cancer patients.Results:IFN-treated monocytes induced caspase 8–dependent apoptosis by the proapoptotic TRAIL and mediated by the death receptors 4 and 5 (DR4 and DR5, respectively) on cancer cells. Therapy was well tolerated with evidence of clinical activity, as 2 of 9 evaluable patients had a partial response by RECIST criteria, and 1 additional patient had a CA-125 response. Upregulation of monocyte-produced TRAIL and cytokines was confirmed in peripheral blood. Long-term responders had alterations in innate and adaptive immune compartments.Conclusions:Given the mechanism of cancer cell death, and the acceptable tolerability of the clinical regimen, this platform presents a possibility for future combination therapies to augment anticancer immunity.See related commentary by Chow and Dorigo, p. 299