title: Comprehensive immunological analyses of colorectal cancer patients in the phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide.
abstract: Dendritic cell (DC) vaccine has been used to treat patients with advanced colorectal cancer (CRC). The results of vaccine-induced clinical responses have not always been satisfactory partially because of DC incompetence. In order to evaluate the feasibility of novel mature DCs for therapeutic adjuvants against CRC, we conducted clinical trials with carcinoembryonic antigen (CEA) peptide-loaded DC quickly generated with a combination of OK432 (Streptococcuspyogenes preparation), prostanoid, and interferon-α (OPA-DC). In the ten patients enrolled in this study, the OPA-DC vaccine was well tolerated and administered four times every 2 weeks except for two patients, who were switched to other treatments due to disease progression. Among the eight evaluable patients, one displayed stable disease (SD), while the remaining seven showed progressive disease (PD). In the SD patient, natural killer (NK) cell frequency and cytolytic activity were increased. In the same patient, the frequency of CEA-specific cytotoxic T cells (CTLs) increased stepwise with repetitive vaccinations; however, most of the CTLs exhibited central memory phenotype. In those with PD, NK cells proliferated well regardless of failure of response, whereas CTLs failed to do so. We concluded that the OPA-DC vaccine is well tolerated and has immune-stimulatory capacity in patients with CRC. Additional modulation is needed to attain significant clinical impact.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Michiyo
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Shoko
authors.initials: S
authors.lastname: Kuroda
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyatake
authors.forename: Ichiyo
authors.initials: I
authors.lastname: Itose
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Naruyasu
authors.initials: N
authors.lastname: Kakita
authors.forename: Koyo
authors.initials: K
authors.lastname: Higashitani
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Matsubara
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Akinori
authors.initials: A
authors.lastname: Kasahara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D010455:Peptides