title: Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer.
abstract: Wilms tumor gene (WT1) protein is an attractive target for cancer immunotherapy. We aimed to investigate the feasibility of a combination therapy consisting of gemcitabine and WT1 peptide-based vaccine for patients with advanced pancreatic cancer and to make initial assessments of its clinical efficacy and immunologic response. Thirty-two HLA-A*24:02 patients with advanced pancreatic cancer were enrolled. Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m) on days 1, 8, and 15 of a 28-day cycle. This combination therapy was well tolerated. The frequencies of grade 3-4 adverse events for this combination therapy were similar to those for gemcitabine alone. Objective response rate was 20.0% (6/30 evaluable patients). Median survival time and 1-year survival rate were 8.1 months and 29%, respectively. The association between longer survival and positive delayed-type hypersensitivity to WT1 peptide was statistically significant, and longer survivors featured a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes both before and after treatment. WT1 vaccine in combination with gemcitabine was well tolerated for patients with advanced pancreatic cancer. Delayed-type hypersensitivity-positivity to WT1 peptide and a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes could be useful prognostic markers for survival in the combination therapy with gemcitabine and WT1 vaccine. Further clinical investigation is warranted to determine the effectiveness of this combination therapy.
authors: Departments of *Cancer Immunotherapy §Surgery †Respiratory Medicine, Allergy and Rheumatic Diseases **Functional Diagnostic Science ∥∥Cancer Stem Cell Biology #Complementary and Alternative Medicine ¶¶Clinical Application of Biologics, Graduate School of Medicine ††Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka Departments of ‡Internal Medicine, Division of Gastroenterology and Hepatology ∥Oncology, Institute of DNA Medicine Departments of ‡‡Surgery §§Pathology, The Jikei University School of Medicine, Tokyo ¶Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Kanagawa ##Department of Young Leaders' Program in Medical Administration, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors: Sumiyuki
authors: S
authors: Nishida
authors: Shigeo
authors: S
authors: Koido
authors: Yutaka
authors: Y
authors: Takeda
authors: Sadamu
authors: S
authors: Homma
authors: Hideo
authors: H
authors: Komita
authors: Akitaka
authors: A
authors: Takahara
authors: Satoshi
authors: S
authors: Morita
authors: Toshinori
authors: T
authors: Ito
authors: Soyoko
authors: S
authors: Morimoto
authors: Kazuma
authors: K
authors: Hara
authors: Akihiro
authors: A
authors: Tsuboi
authors: Yoshihiro
authors: Y
authors: Oka
authors: Satoru
authors: S
authors: Yanagisawa
authors: Yoichi
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authors: Toyama
authors: Masahiro
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authors: Ikegami
authors: Toru
authors: T
authors: Kitagawa
authors: Hidetoshi
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authors: Eguchi
authors: Hiroshi
authors: H
authors: Wada
authors: Hiroaki
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authors: Nagano
authors: Jun
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authors: Nakata
authors: Yoshiki
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authors: Nakae
authors: Naoki
authors: N
authors: Hosen
authors: Yusuke
authors: Y
authors: Oji
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authors: Tanaka
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authors: I
authors: Kawase
authors: Atsushi
authors: A
authors: Kumanogoh
authors: Junichi
authors: J
authors: Sakamoto
authors: Yuichiro
authors: Y
authors: Doki
authors: Masaki
authors: M
authors: Mori
authors: Toshifumi
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authors: Ohkusa
authors: Hisao
authors: H
authors: Tajiri
authors: Haruo
authors: H
authors: Sugiyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002478:Cells, Cultured; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D059871:HLA-A24 Antigen / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007156:Immunologic Memory; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009829:Oleic Acids / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D009829:Oleic Acids; D010446:Peptide Fragments; D025521:Tumor Suppressor Proteins; D022223:Vaccines, Subunit; D003841:Deoxycytidine; C001681:mannide monooleate; D008353:Mannitol; D000093542:Gemcitabine