Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer

Sumiyuki Nishida, Shigeo Koido, Yutaka Takeda, Sadamu Homma, Hideo Komita, Akitaka Takahara, Satoshi Morita, Toshinori Ito, Soyoko Morimoto, Kazuma Hara, Akihiro Tsuboi, Yoshihiro Oka, Satoru Yanagisawa, Yoichi Toyama, Masahiro Ikegami, Toru Kitagawa, Hidetoshi Eguchi, Hiroshi Wada, Hiroaki Nagano, Jun NakataYoshiki Nakae, Naoki Hosen, Yusuke Oji, Toshio Tanaka, Ichiro Kawase, Atsushi Kumanogoh, Junichi Sakamoto, Yuichiro Doki, Masaki Mori, Toshifumi Ohkusa, Hisao Tajiri, Haruo Sugiyama

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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.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalJournal of Immunotherapy
Volume37
Issue number2
DOIs
Publication statusPublished - Feb 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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    Nishida, S., Koido, S., Takeda, Y., Homma, S., Komita, H., Takahara, A., Morita, S., Ito, T., Morimoto, S., Hara, K., Tsuboi, A., Oka, Y., Yanagisawa, S., Toyama, Y., Ikegami, M., Kitagawa, T., Eguchi, H., Wada, H., Nagano, H., ... Sugiyama, H. (2014). Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer. Journal of Immunotherapy, 37(2), 105-114. https://doi.org/10.1097/CJI.0000000000000020