PMID- 31980914
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20200420
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 69
IP  - 4
DP  - 2020 Apr
TI  - First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with 
      NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid 
      tumors.
PG  - 663-675
LID - 10.1007/s00262-020-02483-1 [doi]
AB  - Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York 
      esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) 
      present multiple epitope peptides to the MHC class I and II pathways. Adjuvants 
      are essential for cancer vaccines. MIS416 is a non-toxic microparticle that 
      activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and 
      TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine 
      adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with 
      MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. 
      CHP-NY-ESO-1/MIS416 (mug/mug) was administered at 100/200, 200/200, 200/400 or 
      200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 
      doses (treatment phase) followed by one vaccination every 4 weeks until disease 
      progression or unacceptable toxicity (maintenance phase). The primary endpoints 
      were safety and tolerability, and the secondary endpoint was the immune response. 
      In total, 26 patients were enrolled. Seven patients (38%) continued vaccination 
      in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed 
      in six patients (23%): anorexia and hypertension were observed in one and five 
      patients, respectively. No grade 4-5 drug-related AEs were observed. Eight 
      patients (31%) had stable disease (SD). Neither augmentation of the 
      NY-ESO-1-specific IFN-gamma-secreting CD8(+) T cell response nor an increase in the 
      level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In 
      a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and 
      MIS416 induced significant tumor suppression. This combination therapy is a 
      promising next step.
FAU - Ishihara, Mikiya
AU  - Ishihara M
AUID- ORCID: 0000-0002-7581-2615
AD  - Department of Medical Oncology, Mie University Hospital, 2-174 Edobashi, Tsu, 
      Mie, 514-8507, Japan. mishihara@clin.medic.mie-u.ac.jp.
FAU - Tono, Yasutaka
AU  - Tono Y
AUID- ORCID: 0000-0002-9714-0629
AD  - Department of Medical Oncology, Mie University Hospital, 2-174 Edobashi, Tsu, 
      Mie, 514-8507, Japan.
FAU - Miyahara, Yoshihiro
AU  - Miyahara Y
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, 1577 Kurimamachiya-cho, Tsu, Mie, 514-8507, Japan.
FAU - Muraoka, Daisuke
AU  - Muraoka D
AD  - Department of Oncology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki, Nagasaki, 852-8523, Japan.
FAU - Harada, Naozumi
AU  - Harada N
AD  - United Immunity, Co., Ltd., Room220, Mie University Campus Incubator, 1577 
      Kurimamachiya-cho, Tsu, Mie, 514-8507, Japan.
FAU - Kageyama, Shinichi
AU  - Kageyama S
AD  - Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Sasaki, Takeshi
AU  - Sasaki T
AUID- ORCID: 0000-0002-2458-5686
AD  - Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate 
      School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Hori, Yasuhide
AU  - Hori Y
AUID- ORCID: 0000-0002-0053-995X
AD  - Kameyama Nephro-Urologic Clinic, 1488-215 Sakaemachi, Kameyama, Mie, 519-0111, 
      Japan.
FAU - Soga, Norihito
AU  - Soga N
AD  - Department of Urology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, 
      Nagoya, Aichi, 464-8681, Japan.
FAU - Uchida, Katsunori
AU  - Uchida K
AD  - Department of Pathology, Mie University Graduate School of Medicine, 2-174 
      Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Shiraishi, Taizo
AU  - Shiraishi T
AD  - Department of Pathology, Mie University Graduate School of Medicine, 2-174 
      Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Sato, Eiichi
AU  - Sato E
AD  - Department of Pathology, Institute of Medical Science (Medical Research Center), 
      Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, 
      Japan.
FAU - Kanda, Hideki
AU  - Kanda H
AD  - Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate 
      School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Mizuno, Toshiro
AU  - Mizuno T
AD  - Department of Medical Oncology, Mie University Hospital, 2-174 Edobashi, Tsu, 
      Mie, 514-8507, Japan.
FAU - Webster, Gill A
AU  - Webster GA
AD  - Innate Immunotherapeutics, Melbourne, VIC, 3051, Australia.
FAU - Ikeda, Hiroaki
AU  - Ikeda H
AD  - Department of Oncology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki, Nagasaki, 852-8523, Japan.
FAU - Katayama, Naoyuki
AU  - Katayama N
AD  - Department of Hematology and Oncology, Mie University Graduate School of 
      Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Sugimura, Yoshiki
AU  - Sugimura Y
AD  - Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate 
      School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
FAU - Shiku, Hiroshi
AU  - Shiku H
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, 1577 Kurimamachiya-cho, Tsu, Mie, 514-8507, Japan. 
      shiku@clin.medic.mie-u.ac.jp.
AD  - Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu, Mie, 514-8507, Japan. shiku@clin.medic.mie-u.ac.jp.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20200124
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTAG1B protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (MIS416 vaccine)
RN  - 0 (Membrane Proteins)
RN  - 0 (NOD2 protein, human)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Toll-Like Receptor 9)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Antibodies, Neoplasm/blood/immunology
MH  - Antigens, Neoplasm/*immunology
MH  - CD8-Positive T-Lymphocytes/drug effects/immunology/metabolism
MH  - Cancer Vaccines/administration & dosage/*immunology
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Interferon-gamma/immunology/metabolism
MH  - Male
MH  - Membrane Proteins/*immunology
MH  - Mice, Inbred BALB C
MH  - Middle Aged
MH  - Neoplasms/*immunology/pathology/therapy
MH  - Nod2 Signaling Adaptor Protein/*immunology/metabolism
MH  - Toll-Like Receptor 9/*immunology/metabolism
MH  - Vaccination/methods
PMC - PMC7113205
OTO - NOTNLM
OT  - Cancer vaccine
OT  - NOD2
OT  - NY-ESO-1 antigen
OT  - TLR9
COIS- CHP-NY-ESO-1 was supplied by ImmunoFrontier Inc. (Osaka, Japan). N. Harada is a 
      former employee of ImmunoFrontier Inc. H. Shiku is a stockholder of 
      ImmunoFrontier Inc. MIS416 was supplied by Innate Immunotherapeutics Ltd. 
      (Victoria, Australia). G.A. Webster is an employee of Innate Immunotherapeutics 
      Ltd. The other authors declare that they have no conflicts of interest.
EDAT- 2020/01/26 06:00
MHDA- 2020/04/21 06:00
PMCR- 2020/01/24
CRDT- 2020/01/26 06:00
PHST- 2019/03/22 00:00 [received]
PHST- 2020/01/04 00:00 [accepted]
PHST- 2020/01/26 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2020/01/26 06:00 [entrez]
PHST- 2020/01/24 00:00 [pmc-release]
AID - 10.1007/s00262-020-02483-1 [pii]
AID - 2483 [pii]
AID - 10.1007/s00262-020-02483-1 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2020 Apr;69(4):663-675. doi: 
      10.1007/s00262-020-02483-1. Epub 2020 Jan 24.