PMID- 19604246
OWN - NLM
STAT- MEDLINE
DCOM- 20091009
LR  - 20201215
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 100
IP  - 10
DP  - 2009 Oct
TI  - Phase I clinical study of a peptide vaccination for hepatitis C virus-infected 
      patients with different human leukocyte antigen-class I-A alleles.
PG  - 1935-42
LID - 10.1111/j.1349-7006.2009.01256.x [doi]
AB  - Hepatitis C virus (HCV) infection has a high risk of liver cirrhosis and 
      hepatocellular carcinoma at later stages. We recently identified a peptide 
      derived from the HCV core protein capable of inducing both cellular and humoral 
      responses to nearly all HCV-positive patients in Japan with different human 
      leukocyte antigen (HLA)-class I-A alleles. To assess the safety and immune 
      responses to this novel peptide, we conducted a phase I dose-escalation study of 
      the vaccination for 26 HCV-positive patients who were either non-responders to 
      the interferon-based therapy (n = 23) or refused it (n = 3). The regimen was well 
      tolerated, with no severe vaccine-related toxicity. Twenty-five and 22 patients 
      completed the first and second cycle vaccination (6 and 12 vaccine injections), 
      respectively. After a series of six vaccine injections, peptide-specific CTL 
      activity was augmented in peripheral blood mononuclear cells from 15 of 25 
      patient samples, with an expected optimal dose of 1 mg peptide. After 12 vaccine 
      injections, peptide-specific IgG production was augmented in plasma from the 
      majority of patients (15 of 22 patients) tested, but not in a dose-dependent 
      fashion. There were two HCV RNA responders with >1 log declines. Among patients 
      whose pre-vaccination levels of alanine aminotransferase and alpha feto-protein 
      exceeded the normal ranges, a <30% decrease was found in 7 of 24 and three of six 
      patients, respectively. Because of its tolerability and higher rate of immune 
      boosting, this protocol is recommended for a phase II study to investigate its 
      clinical efficacy.
FAU - Yutani, Shigeru
AU  - Yutani S
AD  - Department of Immunology and Immunotherapy, Kurume University School of Medicine, 
      Kurume, Fukuoka, Japan.
FAU - Komatsu, Nobukazu
AU  - Komatsu N
FAU - Shichijo, Shigeki
AU  - Shichijo S
FAU - Yoshida, Kazumi
AU  - Yoshida K
FAU - Takedatsu, Hiroko
AU  - Takedatsu H
FAU - Itou, Minoru
AU  - Itou M
FAU - Kuromatu, Ryoko
AU  - Kuromatu R
FAU - Ide, Tatsuya
AU  - Ide T
FAU - Tanaka, Masatoshi
AU  - Tanaka M
FAU - Sata, Michio
AU  - Sata M
FAU - Yamada, Akira
AU  - Yamada A
FAU - Itoh, Kyogo
AU  - Itoh K
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090623
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Hepatitis C Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Viral Core Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cancer Vaccines/adverse effects/immunology/*therapeutic use
MH  - Carcinoma, Hepatocellular/*prevention & control/virology
MH  - Female
MH  - HLA-A Antigens/*genetics
MH  - Hepatitis C Antigens/immunology
MH  - Hepatitis C, Chronic/complications/genetics/*therapy
MH  - Humans
MH  - Immunoglobulin G/blood/immunology
MH  - Liver Cirrhosis/prevention & control/virology
MH  - Liver Neoplasms/*prevention & control/virology
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Vaccines, Subunit/immunology/therapeutic use
MH  - Viral Core Proteins/*immunology
EDAT- 2009/07/17 09:00
MHDA- 2009/10/10 06:00
CRDT- 2009/07/17 09:00
PHST- 2009/07/17 09:00 [entrez]
PHST- 2009/07/17 09:00 [pubmed]
PHST- 2009/10/10 06:00 [medline]
AID - CAS1256 [pii]
AID - 10.1111/j.1349-7006.2009.01256.x [doi]
PST - ppublish
SO  - Cancer Sci. 2009 Oct;100(10):1935-42. doi: 10.1111/j.1349-7006.2009.01256.x. Epub 
      2009 Jun 23.