PMID- 25662406
OWN - NLM
STAT- MEDLINE
DCOM- 20150521
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 64
IP  - 4
DP  - 2015 Apr
TI  - Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients 
      with castration-resistant prostate cancer: dose-related immune boosting and 
      suppression.
PG  - 493-505
LID - 10.1007/s00262-015-1660-1 [doi]
AB  - The heterogeneity expression of tumor-associated antigens (TAA) and variability 
      of human T cell repertoire suggest that effective cancer vaccine requires 
      induction of a wide breadth of cytotoxic T lymphocyte (CTL) specificities. This 
      can be achieved with vaccines targeting multiple TAA. We evaluated the safety and 
      immune dynamics of a cancer vaccine consisting of 20 mixed peptides (KRM-20) 
      designed to induce CTLs against 12 different TAA in patients with 
      castration-resistant prostate cancer (CRPC). Patients received each of three 
      different randomly assigned doses of KRM-20 (6, 20, or 60 mg) once a week for 6 
      weeks. KRM-20 was applicable for patients with positive human leukocyte antigen 
      (HLA) A2, A3, A11, A24, A26, A31 or A33 alleles, which cover the majority of the 
      global population. To evaluate the minimum immunological effective dose (MIED), 
      peptide-specific CTL and immunoglobulin G (IgG) responses, and immune suppressive 
      subsets were evaluated during the vaccination. Total of 17 patients was enrolled. 
      No serious adverse drug reactions were encountered. The MIED of KRM-20 in CTL or 
      IgG response calculated by logistic regression model was set as 16 or 1.6 mg, 
      respectively. The frequency of immune suppressive subsets was fewer in the 20 mg 
      cohort than that in 6 or 60 mg cohort. Clinical responses determined by 
      prostate-specific antigen levels were two partial responses (from the 20 mg 
      cohort), five no changes and ten progressive diseases. Twenty milligrams of 
      KRM-20 could be recommended for further studies because of the safety and ability 
      to augment CTL activity.
FAU - Noguchi, Masanori
AU  - Noguchi M
AD  - Division of Clinical Research, Research Center for Innovative Cancer Therapy, 
      Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan, 
      noguchi@med.kurume-u.ac.jp.
FAU - Arai, Gaku
AU  - Arai G
FAU - Matsumoto, Kazumasa
AU  - Matsumoto K
FAU - Naito, Seiji
AU  - Naito S
FAU - Moriya, Fukuko
AU  - Moriya F
FAU - Suekane, Shigetaka
AU  - Suekane S
FAU - Komatsu, Nobukazu
AU  - Komatsu N
FAU - Matsueda, Satoko
AU  - Matsueda S
FAU - Sasada, Tetsuro
AU  - Sasada T
FAU - Yamada, Akira
AU  - Yamada A
FAU - Kakuma, Tatsuyuki
AU  - Kakuma T
FAU - Itoh, Kyogo
AU  - Itoh K
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150207
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Aged
MH  - Antigens, Neoplasm/*immunology
MH  - Biomarkers, Tumor/blood
MH  - Bone Neoplasms/immunology/secondary/*therapy
MH  - CTLA-4 Antigen/blood
MH  - Cancer Vaccines/*administration & dosage
MH  - Cohort Studies
MH  - Follow-Up Studies
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Immunoglobulin G
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Peptide Fragments/*immunology
MH  - Prognosis
MH  - Prostatic Neoplasms, Castration-Resistant/immunology/pathology/*therapy
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC11028456
COIS- K Itoh is a consultant/advisory board member in Green Peptide Co. A.Yamada is a 
      part-time executive of Green Peptide Co. No potential conflict of interest is 
      disclosed by other authors.
EDAT- 2015/02/11 06:00
MHDA- 2015/05/23 06:00
PMCR- 2015/02/07
CRDT- 2015/02/10 06:00
PHST- 2014/07/19 00:00 [received]
PHST- 2015/01/16 00:00 [accepted]
PHST- 2015/02/10 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
PHST- 2015/02/07 00:00 [pmc-release]
AID - 1660 [pii]
AID - 10.1007/s00262-015-1660-1 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2015 Apr;64(4):493-505. doi: 
      10.1007/s00262-015-1660-1. Epub 2015 Feb 7.