Systemic treatment with anti-PD-1 antibody nivolumab in combination with vaccine therapy in advanced pancreatic cancer.

Abstract

3092 Background: Systemic treatment with antibodies against PD-1 has shown promising results in many solid tumors with pancreatic cancer being one of the few exceptions. This may be due to failure of activation and/or recruitment of effector T cells into the tumor. An effective immune response against tumors requires the inhibition of inhibitory signals as well as the activation of antigen specific T-cell response. Thus, therapy efficacy may be improved by combination of anti-PD-1 therapy and dendritic cell vaccines. Methods: Seven patients with stage IV pancreatic cancer included in this pilot study received a treatment with nivolumab and dendritic cells (DC). After isolating monocytes from peripheral blood of the patients, antigen primed MoDC were generated using standard protocols. Nivolumab was given one day before the DC vaccine at a reduced dose of 1-2 mg/kg body weight. Cytokine release of DC and T-cell activity in relation to nivolumab therapy were measured using a standard mixed lymphocyte culture (MLC). Results: Using Recist criteria we observed 2 partial remissions with overall survival after onset of therapy of 13 months and 5 months respectively (at time of abstract submission). Both patients are still alive with an ongoing therapy response. Most patients tolerate the therapy well with only mild side effects upon nivolumab therapy. Cytokine measurement using MLC, showed a change in the cytokine release when nivolumab was added to the culture. Conclusions: At ASCO 2015 we demonstrated that the efficacy of DC based therapy can be improved by blockade of PD-L1 on dendritic cells improving the T-cell specific response. Here we show that systemic anti-PD-1 therapy for patients with pancreatic cancer can be effective even at lower dose when combined with DC vaccine therapy.