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

被引：102

作者：

Koido, Shigeo ^{[1
,2
,3
]}

Homma, Sadamu ^{[3
]}

Okamoto, Masato ^{[7
]}

Takakura, Kazuki ^{[1
]}

Mori, Masako ^{[8
]}

Yoshizaki, Shinji ^{[8
]}

Tsukinaga, Shintaro ^{[1
]}

Odahara, Shunichi ^{[1
]}

Koyama, Seita ^{[4
]}

Imazu, Hiroo ^{[4
]}

Uchiyama, Kan ^{[1
]}

Kajihara, Mikio ^{[1
]}

Arakawa, Hiroshi ^{[4
]}

Misawa, Takeyuki ^{[5
]}

Toyama, Yoichi ^{[5
]}

Yanagisawa, Satoru ^{[5
]}

Ikegami, Masahiro ^{[6
]}

Kan, Shin ^{[3
]}

Hayashi, Kazumi ^{[3
]}

Komita, Hideo ^{[3
]}

Kamata, Yuko ^{[3
]}

Ito, Masaki ^{[3
]}

Ishidao, Takefumi ^{[8
]}

Yusa, Sei-ichi ^{[8
]}

Shimodaira, Shigetaka ^{[9
]}

Gong, Jianlin ^{[11
]}

Sugiyama, Haruo ^{[10
]}

Ohkusa, Toshifumi ^{[1
]}

Tajiri, Hisao ^{[1
]}

机构：

[1] Jikei Univ, Sch Med, Dept Gastroenterol & Hepatol, Dept Internal Med, Kashiwa, Chiba 2778567, Japan

[2] Jikei Univ, Sch Med, Inst Clin Med & Res, Kashiwa, Chiba 2778567, Japan

[3] Jikei Univ, Sch Med, Dept Oncol, Kashiwa, Chiba 2778567, Japan

[4] Jikei Univ, Sch Med, Dept Endoscopy, Kashiwa, Chiba 2778567, Japan

[5] Jikei Univ, Sch Med, Dept Surg, Kashiwa, Chiba 2778567, Japan

[6] Jikei Univ, Sch Med, Dept Pathol, Kashiwa, Chiba 2778567, Japan

[7] Kitasato Univ, Sch Pharm, Dept Adv Immunotherapeut, Tokyo, Japan

[8] Tella Inc, Div Res & Dev, Tokyo, Japan

[9] Shinshu Univ Hosp, Cell Proc Ctr, Nagano, Japan

[10] Osaka Univ, Grad Sch Med, Dept Funct Diagnost Sci, Osaka, Japan

[11] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA

来源：

CLINICAL CANCER RESEARCH | 2014年 / 20卷 / 16期

关键词：

WT1 PEPTIDE VACCINE; CD4(+) T-CELLS; HELPER PEPTIDE; GENE WT1; GEMCITABINE; INDUCTION; PROTEIN; IDENTIFICATION; EXPRESSION; ANTIGENS;

D O I：

10.1158/1078-0432.CCR-14-0314

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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*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. Results: The combination therapy was well tolerated. WT1-specific IFN gamma-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. 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. (C) 2014 AACR.

引用

页码：4228 / 4239

页数：12

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