Details

Autor(en) / Beteiligte

• KOIDO, Shigeo
• HOMMA, Sadamu
• UCHIYAMA, Kan
• KAJIHARA, Mikio
• ARAKAWA, Hiroshi
• MISAWA, Takeyuki
• TOYAMA, Yoichi
• YANAGISAWA, Satoru
• IKEGAMI, Masahiro
• SHIN KAN
• HAYASHI, Kazumi
• KOMITA, Hideo
• OKAMOTO, Masato
• KAMATA, Yuko
• ITO, Masaki
• ISHIDAO, Takefumi
• YUSA, Sei-Ichi
• SHIMODAIRA, Shigetaka
• JIANLIN GONG
• SUGIYAMA, Haruo
• OHKUSA, Toshifumi
• TAJIRI, Hisao
• TAKAKURA, Kazuki
• MORI, Masako
• YOSHIZAKI, Shinji
• TSUKINAGA, Shintaro
• ODAHARA, Shunichi
• KOYAMA, Seita
• IMAZU, Hiroo

Titel

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

Ist Teil von

• Clinical cancer research, 2014-08, Vol.20 (16), p.4228-4239

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.