PMID- 24992895
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20211021
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 16
IP  - 4
DP  - 2014 Jul 3
TI  - Feasibility study of personalized peptide vaccination for metastatic recurrent 
      triple-negative breast cancer patients.
PG  - R70
LID - 10.1186/bcr3685 [doi]
AB  - INTRODUCTION: 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. CLINICAL 
      TRIAL REGISTRATION NUMBER: UMIN000001844 (Registration Date: April 5, 2009).
FAU - Takahashi, Ryuji
AU  - Takahashi R
FAU - Toh, Uhi
AU  - Toh U
FAU - Iwakuma, Nobutaka
AU  - Iwakuma N
FAU - Takenaka, Miki
AU  - Takenaka M
FAU - Otsuka, Hiroko
AU  - Otsuka H
FAU - Furukawa, Mina
AU  - Furukawa M
FAU - Fujii, Teruhiko
AU  - Fujii T
FAU - Seki, Naoko
AU  - Seki N
FAU - Kawahara, Akihiko
AU  - Kawahara A
FAU - Kage, Masayoshi
AU  - Kage M
FAU - Matsueda, Satoko
AU  - Matsueda S
FAU - Akagi, Yoshito
AU  - Akagi Y
FAU - Yamada, Akira
AU  - Yamada A
FAU - Itoh, Kyogo
AU  - Itoh K
FAU - Sasada, Tetsuro
AU  - Sasada T
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140703
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/chemistry/immunology
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Cancer Vaccines/administration & dosage/adverse effects/*immunology
MH  - Feasibility Studies
MH  - Female
MH  - HLA-A Antigens/chemistry/immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunity, Humoral
MH  - Immunotherapy
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Recurrence, Local
MH  - Peptides/*immunology
MH  - Precision Medicine
MH  - Radiography
MH  - Treatment Outcome
MH  - Triple Negative Breast Neoplasms/diagnostic 
      imaging/*immunology/mortality/pathology/*therapy
PMC - PMC4227005
EDAT- 2014/07/06 06:00
MHDA- 2015/06/24 06:00
PMCR- 2014/07/03
CRDT- 2014/07/05 06:00
PHST- 2013/10/08 00:00 [received]
PHST- 2014/06/23 00:00 [accepted]
PHST- 2014/07/05 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
PHST- 2014/07/03 00:00 [pmc-release]
AID - bcr3685 [pii]
AID - 10.1186/bcr3685 [doi]
PST - epublish
SO  - Breast Cancer Res. 2014 Jul 3;16(4):R70. doi: 10.1186/bcr3685.