Abstract 2516: A new generation of dendritic cells to improve cancer therapy shows prolonged progression-free survival in patients with solid tumors

Abstract

Abstract We have previously used different protocols for GMP production of monocyte derived dendritic cells (DCs), loaded them with mRNA and conducted several clinical trials to investigate their therapeutic impact in treatment of different solid tumors like prostate carcinoma, glioblastoma or melanoma. These studies showed that only a group of patients mounted an immune response after DC vaccination within a timeframe of 3 to 6 months. A new generation of IL-12p70 producing DCs gave superior immunological responses in pre-clinical data when compared with DCs generated according to the standard protocol used for DC production so far. Aim one of our study is to show the feasibility of generating IL-12p70 producing monocyte derived DCs with starting material from patients with different types of malignancies in a large scale GMP setting and aim two is to investigate the clinical response of these new generation DCs in patients suffering from different types of cancer and acute myeloid leukemia (AML). Autologous mature DCs were loaded with mRNA (messenger Ribonucleic Acid) either encoding the tumor specific antigens hTERT and survivin, plus where available, autologous tumor mRNA, or the AML specific antigens WT-1 or PRAME. Patients received 4 initial vaccinations in weekly intervals, a delayed type hypersensitivity challenge in week 6 and further boost vaccinations every month. With each vaccination either 2,5 x10^6 or 5×10^6 DCs were injected intradermal. So far we have started treatment of one lung cancer patient, one prostate cancer patient, 4 glioblastoma patients and 3 AML-patients. The lung cancer patient suffering from stage IV disease with lung and brain metastases has now been vaccinated since 12/2011 and remained in stable disease. The glioblastoma patients, also with stage IV diseases, have been vaccinated for 16, 12, 12 and 11 months. All of them are in complete remission. One patient developed a pseudo relapse after 7 and again after 9 months of non-malignant origin. The Prostate cancer patient progressed before an immune response could be expected and immediately dropped out of the vaccination program after start of DC treatment. The first AML patient has started DC treatment in May 2014, the other two just recently and therefore are still too early to evaluate. Our investigations show that mRNA loaded new generation DCs can successfully be produced from patients with different types of cancer. All patients tolerated DC vaccination well. Some patients developed flu-like symptoms on the day of vaccination. Strong DTH responses at the injection sites appeared 2 to 4 days after DC injection from the second vaccination time point on indicating the presence of specific immune responses. Solid tumor patients suffering from advanced disease treated with our DC vaccines have a prolonged progression free survival, showing that this immunotherapeutic approach will be a promising alternative to current standard therapies. Citation Format: Iris Bigalke, Kirsti Honnashagen, Marianne Lundby, Guri Solum, Lisbeth Skoge, Else M. Suso Inderberg, Julitta Kasten, Stein Saboe-Larssen, Dolores J. Schendel, Gunnar Kvalheim. A new generation of dendritic cells to improve cancer therapy shows prolonged progression-free survival in patients with solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2516. doi:10.1158/1538-7445.AM2015-2516