Immunological evaluation of personalized peptide vaccination with gemcitabine for pancreatic cancer.
The aim of the present study was to investigate the safety and immune responses of personalized peptide vaccination when administered with gemcitabine (GEM) in advanced pancreatic cancer (APC) patients. Thirteen patients with APC were enrolled. Pre-vaccination with peripheral blood mononuclear cells and plasma was carried out to examine cellular and humoral responses to 25 or 23 peptides in human leukocyte antigen A24+(+) or A2++(+) patients, respectively. Only the reactive peptides (maximum of four) were then administered weekly at three different dose settings: 1, 2 and 3 mg of peptide. GEM was administered at 1000 mg/m(2) per week for 3 weeks, followed by 1 week of rest. The combination therapy was well tolerated. Grade 3 toxicities were: anemia (three patients), neutropenia (two patients) and thrombocytopenia (two patients). Of these 13 patients, 11 (85%) showed clinical responses, such as reduction in tumor size and/or level of tumor markers. Augmentation of peptide-specific cytotoxic T lymphocyte activity against pancreatic cancer cells was observed at each dose level, whereas the increment of peptide-specific IgG antibodies was dependent on peptide dose. GEM did not inhibit the immune responses induced by personalized peptide vaccinations, and this new type of immunochemotherapy combination is recommended for further clinical study in APC patients.
Yanagimoto
Hiroaki
H
Department of Surgery, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka 573-1191, Japan. yanagimh@hirakata.kmu.ac.jp
Mine
Takashi
T
Yamamoto
Koutaro
K
Satoi
Sohei
S
Terakawa
Naoyoshi
N
Takahashi
Kanji
K
Nakahara
Kimika
K
Honma
Shigenori
S
Tanaka
Masahiro
M
Mizoguchi
Junko
J
Yamada
Akira
A
Oka
Masaaki
M
Kamiyama
Yasuo
Y
Itoh
Kyogo
K
Takai
Soichiro
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000627:therapeutic use*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D003841:Deoxycytidine; D000093542:Gemcitabine