Abstract CT017: Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients

Abstract

Abstract BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects on distant non-irradiated lesions. PATIENTS AND METHODS: In this pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered one week before each cycle. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating PBMCs and serum concentrations of a cytokine panel were sequentially determined before and during treatment. RESULTS: Combined treatment was feasible, safe and well tolerated, without grade 3-4 adverse events. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR and combined treatment. No objective responses were observed, while nine patients (Disease control rate=71%) presented stable disease (five in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-β and IFN-α mRNA in circulating PBMC. Dendritic-cell vaccination increased serum IL-12 and IL-1β concentrations, especially in patients presenting stable disease. CONCLUSIONS: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and provides evidence of immune-associated activity and signs of preliminary clinical efficacy. Citation Format: Maria E. Rodriguez-Ruiz, Jose L. Perez-Gracia, Inmaculada Rodriguez, Carlos Alfaro, Ignacio Gil-Bazo, Alfonso Gurpide, Andres Salazar, Ignacio Melero. Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT017.