Phase I clinical study of a peptide vaccination for hepatitis C virus‐infected patients with different human leukocyte antigen‐class I‐A alleles

• Published in: Cancer science 2009-10, Vol.100 (10), p.1935-1942
• Main Authors: Yutani, Shigeru, Komatsu, Nobukazu, Shichijo, Shigeki, Yoshida, Kazumi, Takedatsu, Hiroko, Itou, Minoru, Kuromatu, Ryoko, Ide, Tatsuya, Tanaka, Masatoshi, Sata, Michio, Yamada, Akira, Itoh, Kyogo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alanine transaminase; Biological and medical sciences; Cancer Vaccines - adverse effects; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Carcinoma, Hepatocellular - prevention & control; Carcinoma, Hepatocellular - virology; Cirrhosis; Core protein; Cytotoxicity; Female; Hepatitis C; Hepatitis C Antigens - immunology; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - therapy; Hepatocellular carcinoma; Histocompatibility antigen HLA; HLA-A Antigens - genetics; Humans; Immune response; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Infection; Liver Cirrhosis - prevention & control; Liver Cirrhosis - virology; Liver Neoplasms - prevention & control; Liver Neoplasms - virology; Lymphocytes T; Male; Medical sciences; Middle Aged; Original; Peripheral blood mononuclear cells; Risk factors; RNA; T-Lymphocytes, Cytotoxic - immunology; Toxicity; Tumors; Vaccination; Vaccines; Vaccines, Subunit - immunology; Vaccines, Subunit - therapeutic use; Viral Core Proteins - immunology
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2009.01256.x

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