title: Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients.
abstract: BACKGROUND
  Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.
  
  
  METHODS
  Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.
  
  
  RESULTS
  No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.
  
  
  CONCLUSIONS
  PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.
  
  
  BACKGROUND
  UMIN000001844 (Registration Date: April 5, 2009).
authors.forename: Ryuji
authors.initials: R
authors.lastname: Takahashi
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Iwakuma
authors.forename: Miki
authors.initials: M
authors.lastname: Takenaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otsuka
authors.forename: Mina
authors.initials: M
authors.lastname: Furukawa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Naoko
authors.initials: N
authors.lastname: Seki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007167:Immunotherapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010455:Peptides / Q000276:immunology*; D057285:Precision Medicine; D011859:Radiography; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D010455:Peptides