title: Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer.
abstract: The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days, with 1- and 2-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of prevaccination factors showed that plasma IL6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR), 1.508, P = 0.043; HR, 1.579, P = 0.024; HR, 0.509, P = 0.002, respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR, 0.231; P = 0.021), suggesting a causal relationship between biologic and clinical efficacy of PPV. On the basis of the safety profile and potential clinical efficacy, we believe that clinical trials of PPV would be warranted for previously treated patients with aCRC.
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kibe
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yutani
authors.affiliation: Department of Surgery and Comprehensive Cancer Control, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.affiliation: Biostatistics Center, Kurume University, Kurume, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.affiliation: Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Hinai
authors.affiliation: Biostatistics Center, Kurume University, Kurume, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Research Center of Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan. Research Center of Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan. Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Japan. tsasada@med.kurume-u.ac.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D019947:Receptors, Interleukin-6 / Q000235:genetics; D019233:Retreatment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019496:Cancer Vaccines; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D022223:Vaccines, Subunit; D002097:C-Reactive Protein