48P - Combined immunotherapy encompassing intratumoral polyICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients. (48P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Renal Cell Cancer
Genitourinary Cancers
Surgical oncology
Radiation oncology
Presenter Maria E. RodrÍguez-Ruiz
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors M.E. RodrÍguez-Ruiz1, J. Perez-Gracia2, I. Rodriguez3, C. Alfaro3, C. Oñate3, G. Perez3, S. Inoges3, L. Resano2, A. Benito4, B. Barbes5, M. Ponz-Sarvisé2, S. Martin Algarra2, A. Gurpide2, M.F. Sanmamed6, C. De Andrea7, J. Echeveste7, A. Salazar8, I. Melero3
  • 1Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 2Oncology, clinica universidad de navarra, 31008 - navarra/ES
  • 3Immunotherapy, clinica universidad de navarra, 31008 - navarra/ES
  • 4Radiology, clinica universidad de navarra, 31008 - navarra/ES
  • 5Radiotherapy, clinica universidad de navarra, 31008 - navarra/ES
  • 6Immunobiology, Yale University School of Medicine, New Haven/US
  • 7Pathology, clinica universidad de navarra, 31008 - navarra/ES
  • 8Immunobiology, Oncovir, 30322 - atlanta/US



Combined tumor immunotherapy interventions have the potential to achieve additive or synergistic effects. Combined local injection of dsRNA analogues (mimicking viral RNA) and repeated vaccination with tumor-lysate loaded dendritic cells shows efficacy against a mouse model of established colon cancer.


In a pilot phase I clinical trial 16 advanced (stage IV) cancer patients received two cycles of a course consisting of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with polyICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each of each cycle, patients received intratumoral image-guided injections of 0.25 mg of Hiltonol. Each cycle was given 3-4 weeks apart and was preceded on day -7 by 600 mg/m2 of cyclophosphamide. The last six patients were given SABR (stereoatactic ablative radiotherapy) in some of the lesions including that injected with Hiltonol. Expression of a series of 25 inmune-relevant genes was sequentially monitored by RT-PCR on circulating PBMCs and serum concentrations of a cytokine panel were sequentially determined.


Combined treatment was feasible, safe and well tolerated without >grade 2 side effects. No objective responses by RECIST1.1 criteria were observed while nine patients experienced stabilization of disease (five of them in the six-patient radiotherapy cohort). A heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to radiotherapy with responding lesions located far from the irradiated region. Response was associated to an increase of CD8 T cells infiltrating the tumor. In this series of patients post-treatment elevated IFNβ and IFNα mRNA in circulating PBMC following intratumoral Hiltonol was detected, in addition to increases of serum IL-12 and IL-1β following DC vaccination, that occurred more prominently in stable disease cases.


This combination strategy aimed to resembling viral infection in tumor tissue, while on a dendritic-cell vaccine approach and added to radiotherapy is safe for advanced cancer patients and shows indications of immune-associated activity.

Clinical trial identification


Legal entity responsible for the study

Clinica Universidad de Navarra




All authors have declared no conflicts of interest.