Vaccination with poly(IC:LC) and peptide-pulsed autologous Dendritic cells in Patients with Pancreatic Cancer

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Summary

This study investigates, DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, as a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). As a result, the treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms.

Patients characteristics

Patients were ≥18 years of age with histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas that was metastatic, locally advanced, or recurrent. Patients were required to have HLA-A2 positivity by serological testing Eastern Cooperative Oncology Group performance status ≤2, expected survival >3 months, measurable disease per RECIST 1.1, and adequate organ function.

Methodology

Peripheral blood monocyte-derived DCs were generated from peripheral blood monocyte (PBMCs)-by performing standard Ficoll-density centrifugation to isolate PBMCs from patient leukaphereses materials. PBMCs were plated in serum free AIM-V CTS media at 2–4 × 108 cells per T225 flask and allowed to adhere for 2 hours in 5% CO2. Medium was replaced with AIM-V containing 25 ng/mL rhIL-4 and 800 IU/mL rhGM-CSF and cultured for 5–7 days at 37 °C, 5% CO2. DCs were cryopreserved in 10% DMSO/5% human albumin at 20 × 106/mL.

On the day of treatment administration, three distinct DC aliquots were separately pulsed with the peptide for an hour and then mixed together before injecting intra-dermally to the patients. The DC injection was followed immediately with intramuscular injection of poly(IC:LC), a toll-like receptor 3 (TLR3) ligand in order to provide a DC maturation signal and enhance expansion of tumor infiltrating T cells.

Treatment

On the day of vaccination, cryopreserved DCs were thawed, washed in AIM-V media, counted, and resuspended to 1 × 106 cells/mL and split into three equal batches. Each batch was pulsed separately with one of the following HLA-A2-binding peptides for 1 hour: 20 μg/ mL of the CEA altered peptide, Cap1-6D, 20 μg/mL of the telomerase peptide: hTERT, or 30 μg/mL of the survivin peptide. At the end of the incubation period, pulsed DCs were pooled, washed and re- suspended to 40 × 106 cells per mL in saline. 1 × 107 antigen-pulsed DCs and poly(IC:LC) were administered to the patient.

Results

Safety and tolerabilityStudy treatment was well tolerated by all patients. However, some patients experienced fatigue and/or flu-like symptoms including fever, myalgia, chills, night sweats, and/or hot flashes. When present, flu-like symptoms generally occurred within 24 hour of poly(IC:LC) administration, and were self- limiting. There was one treatment interruption due to an adverse event in a patient who had treatment held on day 3 due to a grade 2 injection site reaction.
Antitumor activity and survival
Among the eight patients who completed the study, the response at day 56 of four of the individuals was stable disease, while the other half experienced progressive disease. Of the 12 patients who underwent apheresis, the median progression free survival (PFS) was 3.0 months and the median overall survival (OS) was 7.7 months.

Conclusion

This concludes that tumor peptide epitope pulsed autologus DC vaccination in combination with TLR ligands could be a promising approach for controlling tumor growth in pancreatic cancer patients.

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Scientific article publishing date : 4/7/2017

Immucura identifier :BSC21_074EN

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