Abstract LB-163: Immunotherapy utilizing MUC-1-messangerRNA encoding DC and MUC-1 specific CTL in combination with Gemcitabine targeting unresectable or recurrent pancreatic cancer

Abstract

Abstract Background; Mucin1 (MUC1) is known as a mucin core protein expressing in inv asive ductal carcinomas of the pancreas. MUC1-specific cytotoxic T lymphocyt es (CTLs) recognize MUC1 moleculesin a HLA-unrestricted manner. We have prev iously reported that the adoptive immunotherapy (AIT) utilizing MUC1-CTLs stimulated with a MUC1-expressing human pancreatic cancer cell line, named Y PK-1, was useful and safe. We also reported the development of an AIT of MUC 1-CTLs in combination with dendritic cells (DCs) pulsed with MUC1-peptide as well. Here we report that the therapy using DC encoding MUC1-mRNA and MUC1-CTLs targeting unresectable or recurrent pancreatic cancer is safe and effective. Purpose; We assessed whether this immunotherapy is safe and effective. Objective and Methods; Twenty patients with unresectable or recurrent pancreatic cancer had the therapy what we planned, one week later, peripheral blood mononuclear cells (PBMC) were harvested by leukapheresis. The PBMCs were separated and induced to be DCs and CTLs. Matured DCs received MUC-1-mRNA by electroporation, then administrated via subcutaneously. CTLs were co-cultured with YPK-1 pancreatic cancer cell line expressing MUC-1 under the stimulation with IL-2, then administrated via intravenously. Results; Male/Female ratio was 1 to 1 (10/10), Mean age was 60.6 y.o. (37–78), Mean times of administration of cells was 3.35 (1.5–27.9), Mean number of c ells that were administrated was 46 million (DCs) and 1800 million (CTLs), Median observation period was 16.2 months (1.5–27.9). One-year survival rate was 39% (median survival time, 6.9 months). When we focus on the patients with unresectable cancer, their one-year survival rate was 54% (median surviva 1 time, 18.4 months). In addition, patients received DCs of more than 10 million had 58% of one-year survival rate, whereas no patient received less than 10 million's DCs did survive in one year (median survival time, 5.8 months) (p=0.048, Logrank). All of patients received the therapy as outpatients and showed no side effect. Conclusion; First of all, this therapy is quit safe. Second, patients received DCs of more than 10 million had high one-year survival rate suggesting high volume DCs in this combination therapy had high potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2011-LB-163