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 Ohmiya, Yasumasa Niwa, Koji Yamamoto, Toru Kaneko, Mie Nieda, Kiyoshi Yokokawa, Hidemi Goto

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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.

Original languageEnglish
Pages (from-to)e69-e74
JournalPancreas
Volume38
Issue number3
DOIs
Publication statusPublished - 01-04-2009

All Science Journal Classification (ASJC) codes

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

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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., Ohmiya, 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, 38(3), e69-e74. https://doi.org/10.1097/MPA.0b013e318197a9e3