PMID- 31415377
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 98
IP  - 33
DP  - 2019 Aug
TI  - Immune adjuvant therapy using Bacillus Calmette-Guerin cell wall skeleton 
      (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity 
      assessments.
PG  - e16771
LID - 10.1097/MD.0000000000016771 [doi]
LID - e16771
AB  - The cell wall skeleton of Bacillus Calmette-Guerin (BCG-CWS) is a bioactive 
      component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS 
      activates the innate immune system through various pattern recognition receptors 
      and is expected to elicit antigen-specific cellular immune responses when 
      co-administered with tumor antigens. To determine the recommended dose (RD) of 
      BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study 
      of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The 
      primary endpoint was the proportion of treatment-related adverse events (AEs) at 
      each BCG-CWS dose. The secondary endpoints were immune responses and clinical 
      effects. A BCG-CWS dose of 50, 100, or 200 mug/body was administered intradermally 
      on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For 
      the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 
      patients with advanced WT1-expressing cancers refractory to standard anti-cancer 
      therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). 
      Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients 
      at a dose of 200 mug although no serious treatment-related systemic AEs were 
      observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. 
      Some patients demonstrated the induction of the CD4 T cell subset and its 
      differentiation from the naive to memory phenotype, resulting in a tumor 
      response.The RD of BCG-CWS was determined to be 100 mug/body. This dose was well 
      tolerated and showed promising clinical effects with the induction of an 
      appropriate immune response.
FAU - Nishida, Sumiyuki
AU  - Nishida S
AD  - Department of Respiratory Medicine and Clinical Immunology.
FAU - Tsuboi, Akihiro
AU  - Tsuboi A
AD  - Department of Cancer Immunotherapy.
FAU - Tanemura, Atsushi
AU  - Tanemura A
AD  - Department of Dermatology.
FAU - Ito, Toshinori
AU  - Ito T
AD  - Department of Gastroenterological Surgery.
FAU - Nakajima, Hiroko
AU  - Nakajima H
AD  - Department of Cancer Immunology.
FAU - Shirakata, Toshiaki
AU  - Shirakata T
AD  - Department of Cancer Immunotherapy.
FAU - Morimoto, Soyoko
AU  - Morimoto S
AD  - Department of Cancer Immunotherapy.
FAU - Fujiki, Fumihiro
AU  - Fujiki F
AD  - Department of Cancer Immunology.
FAU - Hosen, Naoki
AU  - Hosen N
AD  - Department of Cancer Stem Cell Biology.
FAU - Oji, Yusuke
AU  - Oji Y
AD  - Department of Functional Diagnostic Science, Osaka University Graduate School of 
      Medicine.
FAU - Kumanogoh, Atsushi
AU  - Kumanogoh A
AD  - Department of Respiratory Medicine and Clinical Immunology.
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita, Osaka.
FAU - Kawase, Ichiro
AU  - Kawase I
AD  - Department of Respiratory Medicine and Clinical Immunology.
FAU - Oka, Yoshihiro
AU  - Oka Y
AD  - Department of Respiratory Medicine and Clinical Immunology.
AD  - Department of Cancer Stem Cell Biology.
AD  - Department of Immunopathology, Immunology Frontier Research Center, Osaka 
      University, Suita, Osaka.
FAU - Azuma, Ichiro
AU  - Azuma I
AD  - Hokkaido University, Sapporo.
FAU - Morita, Satoshi
AU  - Morita S
AD  - Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan.
FAU - Sugiyama, Haruo
AU  - Sugiyama H
AD  - Department of Cancer Immunology.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (BCG Vaccine)
RN  - 0 (Cell Wall Skeleton)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage/*therapeutic use
MH  - Adult
MH  - Aged
MH  - BCG Vaccine/administration & dosage/*therapeutic use
MH  - CD4 Lymphocyte Count
MH  - Cell Wall Skeleton/administration & dosage/*therapeutic use
MH  - Colorectal Neoplasms/drug therapy
MH  - Female
MH  - Humans
MH  - Liver Neoplasms/drug therapy
MH  - Lung Neoplasms/drug therapy
MH  - Male
MH  - Melanoma/drug therapy
MH  - Middle Aged
MH  - *Mycobacterium bovis
MH  - Ovarian Neoplasms/drug therapy
MH  - Skin Neoplasms/drug therapy
MH  - Treatment Outcome
PMC - PMC6831317
COIS- All authors declared no potential conflicts of interest with regard to this work.
EDAT- 2019/08/16 06:00
MHDA- 2019/08/28 06:00
PMCR- 2019/08/16
CRDT- 2019/08/16 06:00
PHST- 2019/08/16 06:00 [entrez]
PHST- 2019/08/16 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2019/08/16 00:00 [pmc-release]
AID - 00005792-201908160-00031 [pii]
AID - MD-D-19-01414 [pii]
AID - 10.1097/MD.0000000000016771 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2019 Aug;98(33):e16771. doi: 10.1097/MD.0000000000016771.