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    Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences
    1.
    发明申请
    Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences 审中-公开
    杂种或嵌合多核苷酸，蛋白质和包含乙型肝炎病毒序列的组合物

    公开(公告)号：US20080107693A1

    公开(公告)日：2008-05-08

    申请号：US12004024

    申请日：2007-12-20

    申请人： Huseyin Firat ,  Francois Lemonnier ,  Pierre Langlade-demoyen ,  Marie-Louise Michel ,  Andreas Suhrbier

    发明人： Huseyin Firat ,  Francois Lemonnier ,  Pierre Langlade-demoyen ,  Marie-Louise Michel ,  Andreas Suhrbier

    IPC分类号： A61K39/00 ,  C07H21/04 ,  A61K31/7088 ,  A61P37/04 ,  A61P35/00 ,  C12N15/63

    CPC分类号： C07K14/005 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/292 ,  A61K48/00 ,  A61K2039/5258 ,  A61K2039/57 ,  C07K2319/00 ,  C07K2319/40 ,  C12N2730/10122 ,  C12N2730/10134

    摘要： H-2 class I negative, HLA-A2.1 transgenic 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.

    摘要翻译： 使用H-2级I阴性，HLA-A2.1转基因HHD小鼠进行HLA-A2.1限制性人肿瘤相关CTL表位的免疫原性的比较评估。 在IFA中注射到小鼠中的这些表位肽之间建立了等级关系，其全局与其结合和稳定HLA-A2.1分子的能力相关。 辅助肽的共注射增强了大多数CTL应答。 相比之下，仍然表达自己的I类分子的经典HLA I类转基因小鼠在大多数情况下并不在相同的实验条件下产生H.A.-A2.1限制性CTL应答。 在HHD小鼠中比较了可接受的临床应用的不同单表位免疫策略。 重组的Ty病毒样颗粒或编码与乙型肝炎病毒中膜包膜蛋白融合的表位的DNA得到最好的结果。 使用后一种方法和基于黑素瘤的多表位构建体，可以在单个动物中同时诱导针对五种不同表位的CTL应答。 因此，HHD小鼠为基于肽的癌症免疫治疗的临床前评估提供了通用的动物模型。

    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof
    4.
    发明申请
    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof 有权
    衍生自R9M的突变的免疫原性肽，编码其的多核苷酸及其治疗用途

    公开(公告)号：US20090324556A1

    公开(公告)日：2009-12-31

    申请号：US12314218

    申请日：2008-12-05

    申请人： Huseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  Francois Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    发明人： Huseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  Francois Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    IPC分类号： A61K35/26 ,  C12N5/00

    CPC分类号： C07K14/4748 ,  A61K38/00 ,  A61K39/00

    摘要： The invention concerns the optimization of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukaemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-Ile-Ala-Glu-Czs-Ile-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.

    摘要翻译： 本发明涉及野生R9M肽的优化和所得肽用于人类白血病的治疗性接种和/或预防性接种的用途。 更具体地，本发明涉及衍生自包含野生型R9M肽序列Arg-Ile-Ala-Glu-Cys-Ile-Leu-Gly-Met的人TEL / AML1融合蛋白的突变的免疫原性肽。 本发明还涉及编码突变的R9M免疫原性肽的多核苷酸，包含表达突变的R9M免疫原性肽的核酸序列的细胞表达载体和能够固定在至少一种所述肽/多核苷酸上的多克隆或单克隆抗体。 本发明还涉及所述肽，多核苷酸和/或抗体用于制备疫苗，抗肿瘤药物和组合物以及体内和体内刺激人体免疫应答的用途。