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    Method of enhancing a targeted immune response against tumors
    71.
    发明授权
    Method of enhancing a targeted immune response against tumors 有权
    增强针对肿瘤的靶向免疫应答的方法

    公开(公告)号：US07368116B2

    公开(公告)日：2008-05-06

    申请号：US11090686

    申请日：2005-03-28

    申请人： Jeffrey Schlom ,  Judith Kantor ,  James W. Hodge

    发明人： Jeffrey Schlom ,  Judith Kantor ,  James W. Hodge

    IPC分类号： A61K39/12

    CPC分类号： C07K14/705 ,  A61K39/00 ,  A61K48/00 ,  C07K14/70503 ,  C07K14/70532 ,  C12N2799/021 ,  C12N2799/023 ,  Y02A50/466

    摘要： The present invention is a composition of recombinant virus which has incorporated into its genome or portion thereof a gene encoding an antigen to a disease causing agent and a recombinant virus which has incorporated into its genome or portion thereof a gene encoding an immunostimulatory molecule(s) for the purpose of stimulating an immune response against the disease causing agent. Methods of treatment of diseases such as cancer and diseases caused by pathogenic microorganisms is provide using the composition.

    摘要翻译： 本发明是一种重组病毒的组合物，其在其基因组或其部分中掺入编码抗原的疾病引起剂和重组病毒，所述重组病毒在其基因组或其部分掺入了编码免疫刺激分子的基因， 目的是刺激针对疾病引发剂的免疫应答。 使用该组合物提供治疗由病原微生物引起的癌症和疾病等疾病的方法。

    Recombinant vector expressing multiple costimulatory molecules and uses thereof
    72.
    发明授权
    Recombinant vector expressing multiple costimulatory molecules and uses thereof 有权
    表达多种共刺激分子的重组载体及其用途

    公开(公告)号：US07211432B2

    公开(公告)日：2007-05-01

    申请号：US10406317

    申请日：2003-04-04

    申请人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

    发明人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

    IPC分类号： C12N15/00 ,  C12N15/39 ,  C12N15/19 ,  C12N7/00

    CPC分类号： C12N15/86 ,  A61K35/12 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/57 ,  C07K14/70503 ,  C07K14/70525 ,  C07K14/70528 ,  C07K14/70532 ,  C12N2710/24043 ,  C12N2710/24143 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/464 ,  Y02A50/478

    摘要： The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of these costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater than the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+ and CD8+ T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced antigen-presenting functions.

    摘要翻译： 本发明是编码并表达至少三种或更多共刺激分子的重组载体。 重组载体可另外含有编码一种或多种靶抗原或其免疫表位的基因。 证明了这些共刺激分子对增强的T细胞活化的协同作用。 使用含有编码三个共刺激分子的基因的重组载体的T细胞活化程度远远大于含有一个共刺激分子并且大于使用两个共刺激分子的重组载体构建体的总和。 使用三重共刺激载体的结果在低水平的第一信号或低刺激剂与T细胞比率的条件下最显着。 在分离的CD4 +和/或CD8 + T细胞中都观察到这种现象。 本发明的重组载体可用作抗癌和致病微生物的免疫原和疫苗，以及提供宿主细胞，包括具有增强的抗原呈递功能的树突状细胞和脾细胞。

    Generation of human cytotoxic T-cells specific for carcinoma self-associated antigens and uses thereof
    75.
    发明授权
    Generation of human cytotoxic T-cells specific for carcinoma self-associated antigens and uses thereof 失效
    癌细胞自身抗原特异性的人细胞毒性T细胞的产生及其用途

    公开(公告)号：US6001349A

    公开(公告)日：1999-12-14

    申请号：US396385

    申请日：1995-02-22

    申请人： Dennis L. Panicali ,  Jeffrey Schlom

    发明人： Dennis L. Panicali ,  Jeffrey Schlom

    IPC分类号： C12N15/09 ,  A61K35/76 ,  A61K39/00 ,  A61K39/39 ,  A61K48/00 ,  A61P35/00 ,  C07K14/705 ,  C12N5/10 ,  C12N15/12 ,  A01N63/00

    CPC分类号： C07K14/705 ,  A61K2039/51 ,  A61K39/00 ,  C12N2799/023

    摘要： We have discovered that by using a recombinant DNA viral vector, preferably a pox virus vector having at least one insertion site containing a DNA segment encoding the carcinoma self-associated antigen, or a cytotoxic T-cell eliciting epitope thereof, operably linked to a promoter capable of expression in the host, human cytotoxic T-cells specific for the carcinoma self-associated antigens can be produced. The method preferably comprises introducing a sufficient amount of the recombinant pox virus vector into a host to stimulate production of cytotoxic T-cells, and contacting the host with additional antigen at periodic intervals thereafter. The additional antigen may be added by using a second pox virus vector from a different pox genus. In another embodiment, additional antigen is added by contacting the host with antigen. The antigen may be formulated with an adjuvant or in a liposomal formulation. The T-cells can be isolated. The number of T-cells can be expanded by contacting the isolated cytotoxic T-cells alternately with the carcinoma self-associated antigen or an epitope thereof and IL-2. The isolated T-cells can be used in a method for treating a host having a tumor expressing a carcinoma self-associated antigen comprising introducing cytotoxic T-cells specific for the antigen to the host and at at least one periodic interval thereafter introducing to the host a T-cell eliciting epitope of the carcinoma self-associated antigen.

    摘要翻译： 我们已经发现，通过使用重组DNA病毒载体，优选具有至少一个插入位点的痘病毒载体，所述插入位点含有编码癌自身相关抗原的DNA区段或其启动子的细胞毒性T细胞诱导表位，可操作地连接到启动子 能够在宿主中表达，可以产生对癌自身相关抗原特异性的人细胞毒性T细胞。 该方法优选包括将足够量的重组痘病毒载体引入宿主以刺激细胞毒性T细胞的产生，并且此后以周期性间隔使宿主与另外的抗原接触。 可以通过使用来自不同痘属的第二痘病毒载体添加另外的抗原。 在另一个实施方案中，通过使宿主与抗原接触来加入另外的抗原。 抗原可以用佐剂或脂质体制剂配制。 可以分离T细胞。 可以通过与分离的细胞毒性T细胞与癌自身相关抗原或其表位和IL-2交替接触来扩增T细胞的数量。 分离的T细胞可以用于治疗具有表达癌自身相关抗原的肿瘤的宿主的方法，包括将对抗原特异性的细胞毒性T细胞引入宿主，并且至少在周期性间隔之后向宿主引入 癌自身相关抗原的T细胞引发表位。

    Brachyury polypeptides and methods for use
    76.
    发明授权
    Brachyury polypeptides and methods for use 有权
    Brachyury多肽和使用方法

    公开(公告)号：US08188214B2

    公开(公告)日：2012-05-29

    申请号：US12528796

    申请日：2008-02-27

    申请人： Jeffrey Schlom ,  Claudia M. Palena ,  Andrei P. Kozlov ,  Kwong-yok Tsang

    发明人： Jeffrey Schlom ,  Claudia M. Palena ,  Andrei P. Kozlov ,  Kwong-yok Tsang

    IPC分类号： C07K5/00 ,  A61K38/00 ,  A61K39/00 ,  C12N15/00 ,  C07H21/04

    CPC分类号： C12N15/113 ,  A61K39/00 ,  A61K2039/53 ,  C07K14/4702 ,  C07K14/82 ,  G01N33/56972 ,  G01N33/574 ,  G01N2333/70517 ,  Y02A50/466

    摘要： It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include lung, colon, small intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.

    摘要翻译： 本文公开了Brachyury在人肿瘤中，特别是在小肠，胃，肾，膀胱，子宫，卵巢和睾丸以及肺，结肠和前列腺癌的肿瘤中表达。 免疫原性Brachyury多肽在本文中公开。 这些多肽可用于Brachyury表达的诊断测定，以及用于诱导Brachyury的免疫应答。 提供了编码免疫原性Brachyury多肽的多核苷酸，包括这些多肽的载体，用这些载体转化的宿主细胞，以及使用这些多肽，多核苷酸，载体和宿主细胞的方法。 还提供了诊断Brachyury表达癌症的方法。 示例性的癌症包括肺，结肠，小肠，胃，肾，膀胱，子宫，卵巢，睾丸和前列腺癌。 还公开了治疗癌症的方法。

    Framework residue substituted humanized COL-1 antibodies and their use
    78.
    发明授权
    Framework residue substituted humanized COL-1 antibodies and their use 有权
    框架残基取代人源化COL-1抗体及其用途

    公开(公告)号：US07855276B2

    公开(公告)日：2010-12-21

    申请号：US11813092

    申请日：2005-12-30

    申请人： Syed Kasmiri ,  Rafia Mehdi Kashmiri, legal representative ,  Jeffrey Schlom ,  Eduardo A. Padlan

    发明人： Syed Kasmiri ,  Jeffrey Schlom ,  Eduardo A. Padlan

    IPC分类号： C12P21/08 ,  C07K16/00 ,  A61K39/395 ,  A61K39/00 ,  G01N33/53

    CPC分类号： C07K16/3007 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

    摘要： The present disclosure provides humanized COL-1 monoclonal antibodies that retain CEA binding affinity, compared to a parent antibody. Also disclosed herein are humanized COL-1 monoclonal antibodies that have reduced immunogenicity, compared to a parent antibody. The disclosed humanized COL-1 antibodies include substitution of framework residues with residues from the corresponding positions of a homologous human sequence. In several embodiments, methods are disclosed for the use of a humanized COL-1 antibody in the detection or treatment of a CEA-expressing tumor or cell in a subject. Also disclosed is a kit including the humanized COL-1 antibodies described herein.

    摘要翻译： 本公开提供与亲本抗体相比保留CEA结合亲和力的人源化COL-1单克隆抗体。 本文还公开了与亲本抗体相比具有降低的免疫原性的人源化COL-1单克隆抗体。 公开的人源化COL-1抗体包括用来自同源人序列的相应位置的残基取代框架残基。 在几个实施方案中，公开了使用人源化COL-1抗体检测或治疗受试者中表达CEA的肿瘤或细胞的方法。 还公开了包含本文所述的人源化COL-1抗体的试剂盒。

    Recombinant vector expressing multiple costimulatory molecules and uses thereof
    79.
    发明授权
    Recombinant vector expressing multiple costimulatory molecules and uses thereof 有权
    表达多种共刺激分子的重组载体及其用途

    公开(公告)号：US07771715B2

    公开(公告)日：2010-08-10

    申请号：US11723666

    申请日：2007-03-21

    申请人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

    发明人： Jeffrey Schlom ,  James Hodge ,  Dennis Panicali

    IPC分类号： A61K48/00 ,  C12N15/00

    CPC分类号： C12N15/86 ,  A61K35/12 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/57 ,  C07K14/70503 ,  C07K14/70525 ,  C07K14/70528 ,  C07K14/70532 ,  C12N2710/24043 ,  C12N2710/24143 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/464 ,  Y02A50/478

    摘要： The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of these costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater than the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+ and CD8+ T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced antigen-presenting functions.

    摘要翻译： 本发明是编码并表达至少三种或更多共刺激分子的重组载体。 重组载体可另外含有编码一种或多种靶抗原或其免疫表位的基因。 证明了这些共刺激分子对增强的T细胞活化的协同作用。 使用含有编码三个共刺激分子的基因的重组载体的T细胞活化程度远远大于含有一个共刺激分子并且大于使用两个共刺激分子的重组载体构建体的总和。 使用三重共刺激载体的结果在低水平的第一信号或低刺激剂与T细胞比率的条件下最显着。 用分离的CD4 +和CD8 + T细胞观察到这种现象。 本发明的重组载体可用作抗癌和致病微生物的免疫原和疫苗，以及提供宿主细胞，包括具有增强的抗原呈递功能的树突状细胞和脾细胞。