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Induction of Antigen-Specific Cytotoxic T Lymphocytes by Chemoradiotherapy in Patients Receiving Wilms’ Tumor 1-Targetted Dendritic Cell Vaccinations for Pancreatic Cancer

Shigetaka Shimodaira, Takashi Kobayashi, Koichi Hirabayashi, Kayo Horiuchi, Terutsugu Koya, Yumiko Mizuno, Naoko Yamaoka, Miki Yuzawa, Shinsuke Ishikawa, Yumiko Higuchi, Kenji Sano, Kenichi Ito, and Tomonobu Koizumi

Despite recent advances in cancer treatment, the prognosis of pancreatic cancer (PC) remains poor. Dendritic cells (DCs) play a central role in acquired immunity; therapeutic DC vaccinations have recently been developed for advanced PC. Here we present two cases of PC: inoperable PC localized to the pancreatic head (Case 1, stage IV) and local recurrence complicated by distant metastases following resection of the pancreas body and tail (Case 2, stage III). Both patients received DC vaccinations pulsed with human leukocyte antigen (HLA)-Class I/II-restricted Wilms’ tumor 1 (WT1) peptides during chemoradiotherapy. The induction of WT1 antigen-specific cytotoxic T cells (WT1-CTL) was markedly increased by chemoradiotherapy and was confirmed by measurement of WT1 tetramers and enzyme-linked immunosorbent spot (ELISpot) in both cases. WT1-CTL was found to persist at 1 year without additional DC vaccines in Case 1. In cases 1 and 2, the overall survival (OS) was 32.1 and 24.7 months, respectively, and progression-free survival (PFS) was 25.2 and 8.7 months, respectively. Adverse reactions due to the DC vaccination were tolerable even during chemoradiotherapy, resulting in disease stability. The findings of the present cases may form treatment strategies involving DC vaccination for PC.