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


CONCLUSIONS
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.
Hirooka
Yoshiki
Y
Department of Endoscopy, Nagoya University, Nagoya City, Japan. hirooka@med.nagoya-u.ac.jp
Itoh
Akihiro
A
Kawashima
Hiroki
H
Hara
Kazuo
K
Nonogaki
Koji
K
Kasugai
Toshifumi
T
Ohno
Eizaburo
E
Ishikawa
Takuya
T
Matsubara
Hiroshi
H
Ishigami
Masatoshi
M
Katano
Yoshiaki
Y
Ohmiya
Naoki
N
Niwa
Yasumasa
Y
Yamamoto
Koji
K
Kaneko
Toru
T
Nieda
Mie
M
Yokokawa
Kiyoshi
K
Goto
Hidemi
H
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine