Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences

US7345026B2 · kind B2 · utility

Assignee

• INSTITUT PASTEUR · FR

Inventors

• Hüseyin Firat · Paris, FR
• François Lemonnier · Bourg-la-Reine, FR
• Pierre Langlade-Demoyen · Del Mar, US
• Marie-Louise Michel · Paris, FR
• Andreas Suhrbier · Brisbane, AU

Key dates

• Filing date: Mar 14, 2003
• Grant date: Mar 18, 2008
• Expiry date: Mar 14, 2023

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2730/10134
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

H-2 class I negative, HLA-A2.1 transgeniic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.