TY - JOUR
T1 - A phase i clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer
AU - Suzuki, Nobuaki
AU - Hazama, Shoichi
AU - Ueno, Tomio
AU - Matsui, Hiroto
AU - Shindo, Yoshitaro
AU - Iida, Michihisa
AU - Yoshimura, Kiyoshi
AU - Yoshino, Shigefumi
AU - Takeda, Kazuyoshi
AU - Oka, Masaaki
PY - 2014/1
Y1 - 2014/1
N2 - KIF20A (RAB6KIFL) belongs to the kinesin superfamily of motor proteins, which play critical roles in the trafficking of molecules and organelles during the growth of pancreatic cancer. Immunotherapy using a previously identified epitope peptide for KIF20A is expected to improve clinical outcomes. A phase I clinical trial combining KIF20A-derived peptide with gemcitabine (GEM) was therefore conducted among patients with advanced pancreatic cancer who had received prior therapy such as chemotherapy and/or radiotherapy. GEM was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. The KIF20Aderived peptide was injected subcutaneously on a weekly basis in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body; 3 patients/ cohort). Safety and immunologic parameters were assessed. No severe adverse effects of grade 3 or higher related to KIF20Aderived peptide were observed. Of the 9 patients who completed at least one course of treatment, interferon-γ (IFN-γ)-producing cells were induced in 4 of 9 patients (P2, P3, P6, and P7), and IFN-gproducing cells were increased in 4 of the 9 patients (P1, P5, P8, and P9). Four of the 9 patients achieved stable disease. The disease control rate was 44%. The median survival time after first vaccination was 173 days and 1-year survival rate was 11.1%. IFNg- producing cells were induced by the KIF20A-derived peptide vaccine at a high rate, even in combination with GEM. These results suggest that this combination therapy will be feasible and promising for the treatment of advanced pancreatic cancer.
AB - KIF20A (RAB6KIFL) belongs to the kinesin superfamily of motor proteins, which play critical roles in the trafficking of molecules and organelles during the growth of pancreatic cancer. Immunotherapy using a previously identified epitope peptide for KIF20A is expected to improve clinical outcomes. A phase I clinical trial combining KIF20A-derived peptide with gemcitabine (GEM) was therefore conducted among patients with advanced pancreatic cancer who had received prior therapy such as chemotherapy and/or radiotherapy. GEM was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. The KIF20Aderived peptide was injected subcutaneously on a weekly basis in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body; 3 patients/ cohort). Safety and immunologic parameters were assessed. No severe adverse effects of grade 3 or higher related to KIF20Aderived peptide were observed. Of the 9 patients who completed at least one course of treatment, interferon-γ (IFN-γ)-producing cells were induced in 4 of 9 patients (P2, P3, P6, and P7), and IFN-gproducing cells were increased in 4 of the 9 patients (P1, P5, P8, and P9). Four of the 9 patients achieved stable disease. The disease control rate was 44%. The median survival time after first vaccination was 173 days and 1-year survival rate was 11.1%. IFNg- producing cells were induced by the KIF20A-derived peptide vaccine at a high rate, even in combination with GEM. These results suggest that this combination therapy will be feasible and promising for the treatment of advanced pancreatic cancer.
KW - Immunotherapy
KW - KIF20A
KW - Pancreatic cancer
KW - Peptide
KW - Phase I
UR - http://www.scopus.com/inward/record.url?scp=84890937839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890937839&partnerID=8YFLogxK
U2 - 10.1097/CJI.0000000000000012
DO - 10.1097/CJI.0000000000000012
M3 - Article
C2 - 24316554
AN - SCOPUS:84890937839
SN - 1524-9557
VL - 37
SP - 36
EP - 42
JO - Journal of Biological Response Modifiers
JF - Journal of Biological Response Modifiers
IS - 1
ER -