Abstract 2235: Clinical results of a Phase I/II trial of adjuvant therapeutic vaccination in high risk resected prostate cancer patients using autologous dendritic cells loaded with mRNA from primary prostate cancer tissue, hTERT and survivin
Authors: Tryggestad Anne Merete Aa. , Axcrona Karol , Bigalke Iris , Inderberg-Suso Else M. , Skorstad Gjertrud , Axcrona Ulrika , Aamdal Steinar , Gaudernack Gustav , Schendel Dolores , Lilleby Wolfgang , Dueland Svein , Kvalheim Gunnar 
Published: July 2016

Abstract
Prostate cancer patients diagnosed with high Gleason score (≥ 8) and large tumors (≥T2c) are considered high-risk patients and &gt;50% will develop an early biochemical relapse. Presently, there is no curative therapy available for patients with biochemical relapse. Based on these findings we initiated in January 2011 a Phase I/II dendritic cell (DC) vaccine study. Patients included have pathological stage pT2 - pT3b, Gleason score 7b-10, pN0, pN+ or pNx and postoperative PSA &lt; 0.2 μg/L. Following surgery autologous tumor cell lines were established from each patient using an in-house culturing method. mRNA from the tumor cell line was produced and used for DC vaccination in combination with mRNA hTERT and mRNA Survivin. DCs were differentiated from enriched monocytes, cultured for 2 days with IL4 and GM-CSF and matured with Jonuleit-maturation cocktail for 24 hours. The matured DCs were transfected separately with the 3 different mRNAs and then frozen and stored until use. The vaccination regimen includes one vaccine per week for four weeks, followed by monthly “vaccine boost” during the first year, then every 3 months the second and third year. Recently, a novel 3 days DC protocol using a TLR7/8-agonist maturation cocktail has been implemented at our department. Based on encouraging clinical results with this type of DCs in compassionate use patients with different types of tumors, we decided to change our DCs protocol to the new generation DCs. Of the 20 patients included in this trial 15 patients have been given the standard fast DCs and 5 have been vaccinated with the new type of DCs. 8 Patients given standard DC has completed 3 years of vaccination and 4 has completed 2 years of vaccination. 3 of 15 patient given standard DC has experienced PSA relapse during vaccination. None of the patients given the new type of DC has so far experienced raise in PSA levels. To our knowledge this is the first adjuvant DC vaccine study in high risk prostate cancer and we conclude that the study is feasible, safe and utmost promising. Extensive immune monitoring is ongoing taking advantage of the established autologous tumor cell lines from all patients.
Citation Format: Anne Merete Aa. Tryggestad, Karol Axcrona, Iris Bigalke, Else M. Inderberg-Suso, Gjertrud Skorstad, Ulrika Axcrona, Steinar Aamdal, Gustav Gaudernack, Dolores Schendel, Wolfgang Lilleby, Svein Dueland, Gunnar Kvalheim. Clinical results of a Phase I/II trial of adjuvant therapeutic vaccination in high risk resected prostate cancer patients using autologous dendritic cells loaded with mRNA from primary prostate cancer tissue, hTERT and survivin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2235.