A feasibility and safety study of vaccination with poly-ICLC and peptide-pulsed dendritic cells in patients with metastatic, locally advanced unresectable, or recurrent pancreatic adenocarcinoma.
ABSTRACT
Background: Survival for the pancreatic adenocarcinoma (PC) patients is poor with 5-year survival rate ~6% for all stages combined. Therefore, new therapeutically approaches are urgently needed.
Methods: In this protocol, we generated autologous DCs from peripheral blood monocytes of patients with PC and pulsed the DCs with three immunogenic epitopes expressed by PC cells, namely HLA-A2-restricted peptides derived from human telomerase reverse transcriptase (hTERT, TERT572Y), carcinoembryonic antigen (CEA; Cap1-6D) and survivin (SRV.A2). The novel design of this trial lies in using DCs pulsed with multiple epitopes along with concomitant administration of Poly-ICLC, a Toll-like receptor 3 ligand. Four injections of DC vaccines every 2 weeks with Poly-ICLC. The immune response was measured at each time point of injections by enumerating both phenotype and functions of the effector T cells in a total of 12 patients.
Results: A total of 12 patients were enrolled: 4 male and 8 female. Ten patients were with metastatic PC and 2 patients presented with locally advanced unresectable PC. Primary objective of this study was to assess safety and feasibility, whereas the secondary objective was to determine overall survival, response rate and immunologic response after vaccination. Toxicity was assessed by CTC AE v4.0 and efficacy by RECIST 1.1 criteria. Total of 8 patients were evaluable for toxicity and response. On day 56, 3 patients had stable disease and 5 patients had disease progression. No Grade 3 or 4 treatment related SAE or AE. Grade 1-2 AEs: fatigue (most common), myalgia, fever, injection site reaction, chill, night sweat, hot flashes and abdominal pain. The immunomonitoring data from this study shows an effective expansion in anti-tumor T cells at day 56 (i.e. 14 day after last injection, follow up range 14-56 days).
Conclusions: Vaccination with Poly-ICLC and peptide-pulsed dendritic cells appears to be safe and able to induce a measurable tumor specific T cell population in patients with PC. The immunomonitoring data combined with clinical outcome will be used to design future autologous cell therapeutic trial. Clinical trial information: NCT01410968.