A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer

Yoshiki Hirooka, Akihiro Itoh, Hiroki Kawashima, Kazuo Hara, Koji Nonogaki, Toshifumi Kasugai, Eizaburo Ohno, Takuya Ishikawa, Hiroshi Matsubara, Masatoshi Ishigami, Yoshiaki Katano, Naoki Omiya, Yasumasa Niwa, Koji Yamamoto, Toru Kaneko, Mie Nieda, Kiyoshi Yokokawa, Hidemi Goto

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

OBJECTIVES:: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS:: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS:: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION:: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.

Original languageEnglish
JournalPancreas
Volume38
Issue number3
DOIs
Publication statusPublished - 01-04-2009
Externally publishedYes

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gemcitabine
Pancreatic Neoplasms
Immunotherapy
Cytotoxic T-Lymphocytes
Dendritic Cells
Neoplasm Antigens
Vaccination
Therapeutics
Clinical Trials
Lymphokine-Activated Killer Cells
Cell- and Tissue-Based Therapy
Intravenous Infusions
Intravenous Administration
Needles
Neoplasms
Monoclonal Antibodies
Antigens

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hirooka, Yoshiki ; Itoh, Akihiro ; Kawashima, Hiroki ; Hara, Kazuo ; Nonogaki, Koji ; Kasugai, Toshifumi ; Ohno, Eizaburo ; Ishikawa, Takuya ; Matsubara, Hiroshi ; Ishigami, Masatoshi ; Katano, Yoshiaki ; Omiya, Naoki ; Niwa, Yasumasa ; Yamamoto, Koji ; Kaneko, Toru ; Nieda, Mie ; Yokokawa, Kiyoshi ; Goto, Hidemi. / A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. In: Pancreas. 2009 ; Vol. 38, No. 3.
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abstract = "OBJECTIVES:: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS:: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS:: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION:: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.",
author = "Yoshiki Hirooka and Akihiro Itoh and Hiroki Kawashima and Kazuo Hara and Koji Nonogaki and Toshifumi Kasugai and Eizaburo Ohno and Takuya Ishikawa and Hiroshi Matsubara and Masatoshi Ishigami and Yoshiaki Katano and Naoki Omiya and Yasumasa Niwa and Koji Yamamoto and Toru Kaneko and Mie Nieda and Kiyoshi Yokokawa and Hidemi Goto",
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Hirooka, Y, Itoh, A, Kawashima, H, Hara, K, Nonogaki, K, Kasugai, T, Ohno, E, Ishikawa, T, Matsubara, H, Ishigami, M, Katano, Y, Omiya, N, Niwa, Y, Yamamoto, K, Kaneko, T, Nieda, M, Yokokawa, K & Goto, H 2009, 'A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer', Pancreas, vol. 38, no. 3. https://doi.org/10.1097/MPA.0b013e318197a9e3

A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. / Hirooka, Yoshiki; Itoh, Akihiro; Kawashima, Hiroki; Hara, Kazuo; Nonogaki, Koji; Kasugai, Toshifumi; Ohno, Eizaburo; Ishikawa, Takuya; Matsubara, Hiroshi; Ishigami, Masatoshi; Katano, Yoshiaki; Omiya, Naoki; Niwa, Yasumasa; Yamamoto, Koji; Kaneko, Toru; Nieda, Mie; Yokokawa, Kiyoshi; Goto, Hidemi.

In: Pancreas, Vol. 38, No. 3, 01.04.2009.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer

AU - Hirooka, Yoshiki

AU - Itoh, Akihiro

AU - Kawashima, Hiroki

AU - Hara, Kazuo

AU - Nonogaki, Koji

AU - Kasugai, Toshifumi

AU - Ohno, Eizaburo

AU - Ishikawa, Takuya

AU - Matsubara, Hiroshi

AU - Ishigami, Masatoshi

AU - Katano, Yoshiaki

AU - Omiya, Naoki

AU - Niwa, Yasumasa

AU - Yamamoto, Koji

AU - Kaneko, Toru

AU - Nieda, Mie

AU - Yokokawa, Kiyoshi

AU - Goto, Hidemi

PY - 2009/4/1

Y1 - 2009/4/1

N2 - OBJECTIVES:: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS:: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS:: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION:: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.

AB - OBJECTIVES:: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS:: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS:: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION:: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.

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