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 language | English |
|---|---|
| Journal | Pancreas |
| Volume | 38 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-04-2009 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Hepatology
- Internal Medicine
- Endocrinology
- Endocrinology, Diabetes and Metabolism
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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 journal › Article
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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U2 - 10.1097/MPA.0b013e318197a9e3
DO - 10.1097/MPA.0b013e318197a9e3
M3 - Article
VL - 38
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 3
ER -