PMID- 32500232
OWN - NLM
STAT- MEDLINE
DCOM- 20201022
LR  - 20201022
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 69
IP  - 11
DP  - 2020 Nov
TI  - Exploratory open-label clinical study to determine the S-588410 cancer peptide 
      vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor 
      microenvironment in esophageal cancer patients.
PG  - 2247-2257
LID - 10.1007/s00262-020-02619-3 [doi]
AB  - Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer 
      cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment 
      (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen 
      (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, 
      DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal 
      cancer. This exploratory study investigated the immunologic mechanism of action 
      of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 
      doses) by analyzing the expression of immune-related molecules, cytotoxic 
      T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell 
      receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants 
      with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, 
      CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive 
      (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL 
      response was induced in all patients for at least one of five peptides. The same 
      sequences of peptide-specific TCRs were identified in post-vaccination 
      T-lymphocytes derived from both tumor tissue and blood, suggesting that 
      functional peptide-specific CTLs infiltrate tumor tissue after vaccination. 
      Twelve (80%) participants had treatment-related adverse events (AEs). Injection 
      site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, 
      n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal 
      cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 
      expression in the TME by vaccination suggests S-588410 in combination with 
      anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration 
      UMIN-CTR registration identifier: UMIN000023324.
FAU - Daiko, H
AU  - Daiko H
AUID- ORCID: 0000-0002-9562-2966
AD  - Esophageal Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, 
      Chuo-ku, Tokyo, 104-0045, Japan. hdaiko@ncc.go.jp.
FAU - Marafioti, T
AU  - Marafioti T
AD  - Department of Cellular Pathology, University College London Hospital, London, UK.
FAU - Fujiwara, T
AU  - Fujiwara T
AD  - Department of Gastroenterological Surgery, Okayama University Graduate School of 
      Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Shirakawa, Y
AU  - Shirakawa Y
AD  - Department of Gastroenterological Surgery, Okayama University Graduate School of 
      Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Nakatsura, T
AU  - Nakatsura T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Kato, K
AU  - Kato K
AD  - Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Puccio, I
AU  - Puccio I
AD  - Department of Cellular Pathology, University College London Hospital, London, UK.
FAU - Hikichi, T
AU  - Hikichi T
AD  - R&D Department, Cancer Precision Medicine, Inc., Kawasaki, Japan.
FAU - Yoshimura, S
AU  - Yoshimura S
AD  - R&D Department, Cancer Precision Medicine, Inc., Kawasaki, Japan.
FAU - Nakagawa, T
AU  - Nakagawa T
AD  - Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka, 
      Japan.
FAU - Furukawa, M
AU  - Furukawa M
AD  - Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan.
FAU - Stoeber, K
AU  - Stoeber K
AD  - Business Development, Shionogi & Co., Ltd., London, UK.
FAU - Nagira, M
AU  - Nagira M
AD  - Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka, 
      Japan.
FAU - Ide, N
AU  - Ide N
AD  - Project Management Department, Shionogi & Co., Ltd., Osaka, Japan.
FAU - Kojima, T
AU  - Kojima T
AD  - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer 
      Center Hospital East, Kashiwa, Japan.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200604
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A*24:02 antigen)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Vaccines, Subunit)
SB  - IM
MH  - Aged
MH  - Antigens, Neoplasm/immunology
MH  - Cancer Vaccines/*therapeutic use
MH  - Esophageal Neoplasms/*drug therapy/*immunology
MH  - Female
MH  - HLA-A24 Antigen/immunology
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/drug effects/*immunology
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Cytotoxic/drug effects/*immunology
MH  - Tumor Microenvironment/drug effects/immunology
MH  - Vaccines, Subunit/therapeutic use
PMC - PMC7568713
OTO - NOTNLM
OT  - Cancer peptide vaccine
OT  - Esophageal cancer
OT  - PD-1
OT  - PD-L1
OT  - Tumor-infiltrating lymphocytes
COIS- TK has received travel support from Shionogi & Co., Ltd. in relation to this 
      study and grants from Ono Pharmaceuticals, Merck, Sharpe & Dohme, Oncolys 
      BioPharma, Astellas Amgen BioPharma and Chugai, outside the submitted work. KK 
      has received grants from Ono Pharmaceuticals, Merck & Co. and Merck Serono. T 
      Nakatsura undertakes advisory services for Shionogi Co., Ltd. YS has received 
      travel support from Shionogi & Co., Ltd in relation to this study. TM has 
      undertaken speaker's bureau for Ventana/Roche and Gilead Sciences Ltd., receives 
      royalties relating to patents from DAKO Agilent and has received travel support 
      from Ventana/Roche. TM and IP have a patent pending for a multiplex IHC protocol. 
      TH and SY are employees of Cancer Precision Medicine, Inc., and hold patents that 
      have been licensed to OncoTherapy Science, Inc. T Nakagawa, MF, MN, KS and NI are 
      employees of Shionogi Co., Ltd. HD and TF declare no conflicts of interest.
EDAT- 2020/06/06 06:00
MHDA- 2020/10/23 06:00
PMCR- 2020/06/04
CRDT- 2020/06/06 06:00
PHST- 2020/02/27 00:00 [received]
PHST- 2020/05/20 00:00 [accepted]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2020/10/23 06:00 [medline]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2020/06/04 00:00 [pmc-release]
AID - 10.1007/s00262-020-02619-3 [pii]
AID - 2619 [pii]
AID - 10.1007/s00262-020-02619-3 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2020 Nov;69(11):2247-2257. doi: 
      10.1007/s00262-020-02619-3. Epub 2020 Jun 4.