PMID- 29969453
OWN - NLM
STAT- MEDLINE
DCOM- 20181227
LR  - 20190312
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 7
DP  - 2018
TI  - Development of a novel immunoproteasome digestion assay for synthetic long 
      peptide vaccine design.
PG  - e0199249
LID - 10.1371/journal.pone.0199249 [doi]
LID - e0199249
AB  - Recently, many autologous tumor antigens have been examined for their potential 
      use in cancer immunotherapy. However, the success of cancer vaccines in clinical 
      trials has been limited, partly because of the limitations of using single, short 
      peptides in most attempts. With this in mind, we aimed to develop multivalent 
      synthetic long peptide (SLP) vaccines containing multiple cytotoxic T-lymphocyte 
      (CTL) epitopes. However, to confirm whether a multivalent vaccine can induce an 
      individual epitope-specific CTL, the only viable screening strategies currently 
      available are interferon-gamma (IFN-gamma enzyme-linked immunospot (ELISPOT) assays 
      using human peripheral blood mononuclear cells, or expensive human leukocyte 
      antigen (HLA)-expressing mice. In this report, we evaluated the use of our 
      developed murine-20S immunoproteasome (i20S) digestion assay, and found that it 
      could predict the results of IFN-gamma ELISPOT assays. Importantly, the murine-i20S 
      digestion assay not only predicted CTL induction, but also antitumor activity in 
      an HLA-expressing mouse model. We conclude that the murine-i20S digestion assay 
      is an extremely useful tool for the development of "all functional" multivalent 
      SLP vaccines.
FAU - Wada, Hiroshi
AU  - Wada H
AUID- ORCID: 0000-0003-0158-1743
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
FAU - Shimizu, Atsushi
AU  - Shimizu A
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
FAU - Osada, Toshihiro
AU  - Osada T
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
FAU - Tanaka, Yuki
AU  - Tanaka Y
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
FAU - Fukaya, Satoshi
AU  - Fukaya S
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
FAU - Sasaki, Eiji
AU  - Sasaki E
AD  - Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd., 
      Tsukuba, Ibaraki, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180703
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Vaccines, Subunit)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
EIN - PLoS One. 2018 Oct 4;13(10):e0205567. PMID: 30286206
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cancer Vaccines/chemical synthesis/immunology/*pharmacology
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitopes, T-Lymphocyte/chemistry/immunology
MH  - HLA-A2 Antigen/*genetics/immunology
MH  - Humans
MH  - *Immunoassay
MH  - Immunotherapy, Active/*methods
MH  - Interferon-gamma/biosynthesis/immunology
MH  - Lymphocyte Activation/drug effects
MH  - Melanoma, Experimental/genetics/immunology/pathology/*prevention & control
MH  - Mice
MH  - Mice, Transgenic
MH  - Peptides/chemical synthesis/immunology/*pharmacology
MH  - Proteasome Endopeptidase Complex/genetics/immunology
MH  - T-Lymphocytes, Cytotoxic/cytology/drug effects/immunology
MH  - Transgenes
MH  - Tumor Burden/drug effects
MH  - Vaccines, Subunit
PMC - PMC6029771
COIS- All of the authors are salaried employee of the Taiho Pharmaceutical Co. 
      Ltd.However, this does not alter our adherence to PLOS ONE policies on sharing 
      data and materials.
EDAT- 2018/07/04 06:00
MHDA- 2018/12/28 06:00
PMCR- 2018/07/03
CRDT- 2018/07/04 06:00
PHST- 2017/12/04 00:00 [received]
PHST- 2018/06/04 00:00 [accepted]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2018/12/28 06:00 [medline]
PHST- 2018/07/03 00:00 [pmc-release]
AID - PONE-D-17-42577 [pii]
AID - 10.1371/journal.pone.0199249 [doi]
PST - epublish
SO  - PLoS One. 2018 Jul 3;13(7):e0199249. doi: 10.1371/journal.pone.0199249. 
      eCollection 2018.