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Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection.
Jacobson, Jeffrey M; Zahrieh, David; Strand, Carrie A; Cruz-Correa, Marcia; Pungpapong, Surakit; Roberts, Lewis R; Mandrekar, Sumithra J; Rodriguez, Luz Maria; Boyer, Jean; Marrero, Idania; Kraynyak, Kimberly A; Morrow, Matthew P; Sylvester, Albert J; Pawlicki, Jan M; Gillespie, Elisabeth; Barranco, Eduardo; Richmond, Ellen; Umar, Asad; Weiner, David B; Limburg, Paul J.
Afiliação
  • Jacobson JM; Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Zahrieh D; Mayo Clinic, Rochester, Minnesota.
  • Strand CA; Mayo Clinic, Rochester, Minnesota.
  • Cruz-Correa M; University of Puerto Rico, San Juan, Puerto Rico.
  • Pungpapong S; Mayo Clinic, Jacksonville, Florida.
  • Roberts LR; Mayo Clinic, Rochester, Minnesota.
  • Mandrekar SJ; Mayo Clinic, Rochester, Minnesota.
  • Rodriguez LM; National Cancer Institute, Division of Cancer Prevention, Rockville, Maryland.
  • Boyer J; Walter Reed National Military Medical Center, Department of Surgery, Bethesda, Maryland.
  • Marrero I; Inovio Pharmaceuticals, San Diego, California.
  • Kraynyak KA; Inovio Pharmaceuticals, San Diego, California.
  • Morrow MP; Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.
  • Sylvester AJ; Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.
  • Pawlicki JM; Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.
  • Gillespie E; Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.
  • Barranco E; Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.
  • Richmond E; Inovio Pharmaceuticals, San Diego, California.
  • Umar A; National Cancer Institute, Division of Cancer Prevention, Rockville, Maryland.
  • Weiner DB; National Cancer Institute, Division of Cancer Prevention, Rockville, Maryland.
  • Limburg PJ; Wistar Institute, Philadelphia, Pennsylvania.
Cancer Prev Res (Phila) ; 16(3): 163-173, 2023 03 01.
Article em En | MEDLINE | ID: mdl-36534786
ABSTRACT
Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry-based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia. PREVENTION RELEVANCE The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hepatite C / Carcinoma Hepatocelular / Vacinas de DNA / Hepatite C Crônica / Neoplasias Hepáticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hepatite C / Carcinoma Hepatocelular / Vacinas de DNA / Hepatite C Crônica / Neoplasias Hepáticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article