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Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer

This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pu...

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Autores principales: Mayanagi, Shuhei, Kitago, Minoru, Sakurai, Toshiharu, Matsuda, Tatsuo, Fujita, Tomonobu, Higuchi, Hajime, Taguchi, Junichi, Takeuchi, Hiroya, Itano, Osamu, Aiura, Koichi, Hamamoto, Yasuo, Takaishi, Hiromasa, Okamoto, Masato, Sunamura, Makoto, Kawakami, Yutaka, Kitagawa, Yuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409883/
https://www.ncbi.nlm.nih.gov/pubmed/25614082
http://dx.doi.org/10.1111/cas.12621
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author Mayanagi, Shuhei
Kitago, Minoru
Sakurai, Toshiharu
Matsuda, Tatsuo
Fujita, Tomonobu
Higuchi, Hajime
Taguchi, Junichi
Takeuchi, Hiroya
Itano, Osamu
Aiura, Koichi
Hamamoto, Yasuo
Takaishi, Hiromasa
Okamoto, Masato
Sunamura, Makoto
Kawakami, Yutaka
Kitagawa, Yuko
author_facet Mayanagi, Shuhei
Kitago, Minoru
Sakurai, Toshiharu
Matsuda, Tatsuo
Fujita, Tomonobu
Higuchi, Hajime
Taguchi, Junichi
Takeuchi, Hiroya
Itano, Osamu
Aiura, Koichi
Hamamoto, Yasuo
Takaishi, Hiromasa
Okamoto, Masato
Sunamura, Makoto
Kawakami, Yutaka
Kitagawa, Yuko
author_sort Mayanagi, Shuhei
collection PubMed
description This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2)) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well-tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them. WT1 peptide-pulsed DCGEM is feasible and effective for inducing anti-tumor T-cell responses. Our results support future investigations for pancreatic cancer patients with non-liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855).
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spelling pubmed-44098832015-10-05 Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer Mayanagi, Shuhei Kitago, Minoru Sakurai, Toshiharu Matsuda, Tatsuo Fujita, Tomonobu Higuchi, Hajime Taguchi, Junichi Takeuchi, Hiroya Itano, Osamu Aiura, Koichi Hamamoto, Yasuo Takaishi, Hiromasa Okamoto, Masato Sunamura, Makoto Kawakami, Yutaka Kitagawa, Yuko Cancer Sci Original Articles This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2)) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well-tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them. WT1 peptide-pulsed DCGEM is feasible and effective for inducing anti-tumor T-cell responses. Our results support future investigations for pancreatic cancer patients with non-liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855). BlackWell Publishing Ltd 2015-04 2015-03-09 /pmc/articles/PMC4409883/ /pubmed/25614082 http://dx.doi.org/10.1111/cas.12621 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Mayanagi, Shuhei
Kitago, Minoru
Sakurai, Toshiharu
Matsuda, Tatsuo
Fujita, Tomonobu
Higuchi, Hajime
Taguchi, Junichi
Takeuchi, Hiroya
Itano, Osamu
Aiura, Koichi
Hamamoto, Yasuo
Takaishi, Hiromasa
Okamoto, Masato
Sunamura, Makoto
Kawakami, Yutaka
Kitagawa, Yuko
Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title_full Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title_fullStr Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title_full_unstemmed Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title_short Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
title_sort phase i pilot study of wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409883/
https://www.ncbi.nlm.nih.gov/pubmed/25614082
http://dx.doi.org/10.1111/cas.12621
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