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  • Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.

Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research (2014-07-25)
Shigeo Koido, Sadamu Homma, Masato Okamoto, Kazuki Takakura, Masako Mori, Shinji Yoshizaki, Shintaro Tsukinaga, Shunichi Odahara, Seita Koyama, Hiroo Imazu, Kan Uchiyama, Mikio Kajihara, Hiroshi Arakawa, Takeyuki Misawa, Yoichi Toyama, Satoru Yanagisawa, Masahiro Ikegami, Shin Kan, Kazumi Hayashi, Hideo Komita, Yuko Kamata, Masaki Ito, Takefumi Ishidao, Sei-Ichi Yusa, Shigetaka Shimodaira, Jianlin Gong, Haruo Sugiyama, Toshifumi Ohkusa, Hisao Tajiri
ABSTRACT

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. Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*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. The combination therapy was well tolerated. WT1-specific IFNγ-producing CD4(+) 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 DTH-positive 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human IFNA1 / Interferon Alpha-1/13 ELISA Kit, for serum, plasma, cell culture supernatants and urine
Sigma-Aldrich
Human IFN γ ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Human IFN γ ELISA Kit, for cell and tissue lysates