Treatment with Chemotherapy and Dendritic Cells Pulsed with Multiple Wilms' Tumor 1 (WT1)-Specific MHC Class I/II-Restricted Epitopes for Pancreatic Cancer

S. Koido, S. Homma, M. Okamoto, K. Takakura, M. Mori, S. Yoshizaki, S. Tsukinaga, S. Odahara, S. Koyama, H. Imazu, K. Uchiyama, M. Kajihara (+17 others)
2014 Clinical Cancer Research  
Purpose: We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II-restricted epitopes, in combination with chemotherapy. Experimental Design: Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A Ã
more » ... 2:01, A Ã 02:06, A Ã 24:02, DRB1 Ã 04:05, DRB1 Ã 08:03, DRB1 Ã 15:01, DRB1 Ã 15:02, DPB1 Ã 05:01, or DPB1 Ã 09:01 were enrolled. The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1-II; 1 PDA), or I/II-restricted WT1 peptides (DC/WT1-I/II; 7 PDA), and gemcitabine. Results: The combination therapy was well tolerated. WT1-specific IFNg-producing CD4 þ T cells were significantly increased following treatment with DC/WT1-I/II. WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The WT1-specific DTHpositive patients showed significantly improved overall survival (OS) and progression-free survival (PFS) compared with the negative control patients. In particular, all 3 patients with PDA with strong DTH reactions had a median OS of 717 days. Conclusions: The activation of WT1-specific immune responses by DC/WT1-I/II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer. Clin Cancer Res; 20(16); 4228-39. Ó2014 AACR.
doi:10.1158/1078-0432.ccr-14-0314 pmid:25056373 fatcat:hf37hiwha5bw5g7ymlsjhsuqs4