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    Peptides recognized by melanoma-specific cytotoxic lymphocytes, and uses therefor
    1.
    发明授权
    Peptides recognized by melanoma-specific cytotoxic lymphocytes, and uses therefor 失效
    由黑素瘤特异性细胞毒性淋巴细胞识别的肽及其用途

    公开(公告)号：US06660276B1

    公开(公告)日：2003-12-09

    申请号：US08234784

    申请日：1994-04-29

    申请人： Craig L. Slingluff ,  Victor M. Engelhard ,  Donald F. Hunt ,  Jeffrey Shabanowitz ,  Andrea L. Cox

    发明人： Craig L. Slingluff ,  Victor M. Engelhard ,  Donald F. Hunt ,  Jeffrey Shabanowitz ,  Andrea L. Cox

    IPC分类号： A61K3900

    CPC分类号： C12Y110/03001 ,  A61K39/00 ,  C07K14/4748 ,  C12N9/0059

    摘要： The instant disclosure identifies and synthesizes peptide residues initially isolated from a melanoma cell line. The peptides are capable of reconstituting an epitope recognized by tumor specific CTL. Some of the sequences are homologous with proteins identified as pMEL17, tyrosinase and cofilin. The present invention provides for the treatment of melanoma patients using synthetic peptides that reconstitute epitopes for melanoma specific CTL. In another embodiment the peptides are used as vaccines for imparting immunity. Alternatively, in one embodiment the peptides may be used to bind to antigen presenting cells in a method for providing specific antigenic stimulation of CTL. The instant invention provides CTL cell lines capable of recognizing reconstituted HLA-A2.1 epitopes and their use in methods of adoptive immunotherapy. The invention additionally provides for genes encoding for peptides capable of reconstituting epitopes recognized by tumor specific CTL and their use as vaccines in the prevention and management of melanoma. A splitter is also disclosed to identify active peptides.

    摘要翻译： 本公开确定并合成最初从黑素瘤细胞系分离的肽残基。 这些肽能够重组由肿瘤特异性CTL识别的表位。 一些序列与鉴定为pMEL17，酪氨酸酶和cofilin的蛋白质同源。 本发明提供使用重构黑色素瘤特异性CTL表位的合成肽治疗黑素瘤患者。 在另一个实施方案中，肽用作赋予免疫力的疫苗。 或者，在一个实施方案中，肽可以用于在用于提供CTL的特异性抗原刺激的方法中与抗原呈递细胞结合。 本发明提供能够识别重组的HLA-A2.1表位的CTL细胞系及其在过继性免疫治疗方法中的用途。 本发明另外提供编码能够重组由肿瘤特异性CTL识别的表位的肽的基因及其在预防和治疗黑素瘤中作为疫苗的用途。 还公开了一种分离器来鉴定活性肽。

    Apparatus for producing ions of thermally labile or nonvolatile solids
    3.
    发明授权
    Apparatus for producing ions of thermally labile or nonvolatile solids 失效

    公开(公告)号：US4156814A

    公开(公告)日：1979-05-29

    申请号：US822216

    申请日：1977-08-05

    申请人： Donald F. Hunt ,  Jeffrey Shabanowitz

    发明人： Donald F. Hunt ,  Jeffrey Shabanowitz

    IPC分类号： H01J49/04 ,  H01J49/14

    CPC分类号： H01J49/0409 ,  H01J49/142

    摘要： An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.

    Apparatus for producing ions of thermally labile or nonvolatile solids
    4.
    发明授权
    Apparatus for producing ions of thermally labile or nonvolatile solids 失效
    用于产生热不稳定或非挥发性固体的离子的装置

    公开(公告)号：US4175234A

    公开(公告)日：1979-11-20

    申请号：US916151

    申请日：1978-06-16

    申请人： Donald F. Hunt ,  Jeffrey Shabanowitz

    发明人： Donald F. Hunt ,  Jeffrey Shabanowitz

    IPC分类号： H01J49/14 ,  H01J49/16 ,  H01J27/00

    CPC分类号： H01J49/145 ,  H01J49/16

    摘要： An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.

    摘要翻译： 一种用于离子化和蒸发样品的非挥发性或热不稳定分子的装置，用于引入质谱仪分析仪，其包括含有电离室的壳体; 离子出口，用于将气态离子从所述电离室引入质谱仪分析仪，所述质谱仪分析仪附着在所述质谱仪分析仪上​​; 用于将气体反应物引入所述壳体内的所述电离室的入口装置; 入口装置，用于将高能量辐射进入所述壳体内的所述电离室，以使所述气态反应物的分子至少部分电离; 开口意味着通向所述壳体的所述电离室，用​​于允许导电发射器，其特征在于具有高度不规则表面的导电元件，在其上沉积所述样品用于分析所述质谱仪分析仪; 以及所述壳体中的真空出口孔，通过该真空出口孔可以减小所述电离室内的压力。

    Method and apparatus for generation of reagent ions in a mass spectrometer
    6.
    发明授权
    Method and apparatus for generation of reagent ions in a mass spectrometer 有权
    用于在质谱仪中产生试剂离子的方法和装置

    公开(公告)号：US08119984B2

    公开(公告)日：2012-02-21

    申请号：US12473570

    申请日：2009-05-28

    申请人： Jeffrey Shabanowitz ,  Philip D. Compton ,  Lee Earley ,  George C. Stafford, Jr. ,  Donald F. Hunt ,  Christopher Mullen

    发明人： Jeffrey Shabanowitz ,  Philip D. Compton ,  Lee Earley ,  George C. Stafford, Jr. ,  Donald F. Hunt ,  Christopher Mullen

    IPC分类号： H01J49/10

    CPC分类号： H01J49/12 ,  H01J49/0072

    摘要： A front-end reagent ion source for a mass spectrometer is disclosed. Reagent vapor is supplied to a reagent ionization volume located within a chamber of the mass spectrometer and maintained at a low vacuum pressure. Reagent ions are formed by interaction of the reagent vapor molecules with an electrical discharge (e.g., a glow discharge) within the ionization volume, and pass into the chamber of the mass spectrometer. At least one ion optical element located along the analyte ion path transports the reagent ions to successive chambers of the mass spectrometer. The reagent ions may be combined with the analyte ions to perform ion-ion studies such as electron transfer dissociation (ETD).

    摘要翻译： 公开了用于质谱仪的前端试剂离子源。 将试剂蒸气供给到位于质谱仪室内的试剂电离体并保持在低真空压力下。 试剂离子通过试剂蒸气分子与离子化体积内的放电（例如，辉光放电）的相互作用而形成，并进入质谱仪的室。 沿着分析物离子路径定位的至少一个离子光学元件将试剂离子输送到质谱仪的连续室。 试剂离子可与分析物离子组合以进行离子离子研究，例如电子转移离解（ETD）。

    Method and Apparatus for Generation of Reagent Ions in a Mass Spectrometer
    8.
    发明申请
    Method and Apparatus for Generation of Reagent Ions in a Mass Spectrometer 有权
    用于在质谱仪中产生试剂离子的方法和装置

    公开(公告)号：US20090294649A1

    公开(公告)日：2009-12-03

    申请号：US12473570

    申请日：2009-05-28

    申请人： Jeffrey Shabanowitz ,  Philip D. Compton ,  Lee Earley ,  George C. Stafford, JR. ,  Donald F. Hunt ,  Christopher Mullen

    发明人： Jeffrey Shabanowitz ,  Philip D. Compton ,  Lee Earley ,  George C. Stafford, JR. ,  Donald F. Hunt ,  Christopher Mullen

    IPC分类号： B01D59/44 ,  H01J49/00 ,  H01J27/00

    CPC分类号： H01J49/12 ,  H01J49/0072

    摘要： A front-end reagent ion source for a mass spectrometer is disclosed. Reagent vapor is supplied to a reagent ionization volume located within a chamber of the mass spectrometer and maintained at a low vacuum pressure. Reagent ions are formed by interaction of the reagent vapor molecules with an electrical discharge (e.g., a glow discharge) within the ionization volume, and pass into the chamber of the mass spectrometer. At least one ion optical element located along the analyte ion path transports the reagent ions to successive chambers of the mass spectrometer. The reagent ions may be combined with the analyte ions to perform ion-ion studies such as electron transfer dissociation (ETD).

    摘要翻译： 公开了用于质谱仪的前端试剂离子源。 将试剂蒸气供给到位于质谱仪室内的试剂电离体并保持在低真空压力下。 试剂离子通过试剂蒸气分子与离子化体积内的放电（例如，辉光放电）的相互作用而形成，并进入质谱仪的室。 沿着分析物离子路径定位的至少一个离子光学元件将试剂离子输送到质谱仪的连续室。 试剂离子可与分析物离子组合以进行离子离子研究，例如电子转移离解（ETD）。

    Phosphopeptides as melanoma vaccines
    9.
    发明授权
    Phosphopeptides as melanoma vaccines 有权
    磷酸肽作为黑素瘤疫苗

    公开(公告)号：US09279011B2

    公开(公告)日：2016-03-08

    申请号：US13318821

    申请日：2010-05-04

    申请人： Suzanne L. Topalian ,  Florence A Depontieu ,  Donald F. Hunt ,  Jeffrey Shabanowitz ,  Jie Qian ,  Victor H. Engelhard ,  Angela Lee Zarling

    发明人： Suzanne L. Topalian ,  Florence A Depontieu ,  Donald F. Hunt ,  Jeffrey Shabanowitz ,  Jie Qian ,  Victor H. Engelhard ,  Angela Lee Zarling

    IPC分类号： A61K39/00 ,  A61K47/00 ,  C07K14/47 ,  G01N33/574 ,  C12Q1/68 ,  A61K39/39

    CPC分类号： C07K14/4748 ,  A61K39/0011 ,  A61K39/39 ,  A61K2039/5154 ,  A61K2039/5158 ,  G01N33/5743

    摘要： We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints”. We generated HLA-DRβ1*0101-restricted CD4+ T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4+ T cells are potential targets for cancer immunotherapy.

    摘要翻译： 我们使用顺序亲和分离，生物化学富集，质谱测序和比较分析鉴定了总共175个HLA-DR相关磷酸肽。 许多来源于可能在癌症发展，生长和转移中起作用的源蛋白质。 大多数仅由黑素瘤或转化的B细胞表达，表明定义细胞类型特异性磷酸酯“指纹”的潜力。 我们产生HLA-DR和bgr。1 * 0101限制性CD4 + T细胞，特异于在两个黑素瘤细胞系中鉴定的磷酸化MART-1肽。 这些T细胞对磷酸肽脉冲的抗原呈递细胞以及完整的黑素瘤细胞显示出特异性。 人CD4 + T细胞可识别的MHC II限制性磷酸肽是癌症免疫治疗的潜在靶标。

    Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof
    10.
    发明授权
    Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof 有权
    1型糖尿病中流行的病原性T细胞靶向的抗原及其用途

    公开(公告)号：US08758767B2

    公开(公告)日：2014-06-24

    申请号：US10557273

    申请日：2004-05-20

    申请人： Teresa P. DiLorenzo ,  Anne M. Evans ,  Donald F. Hunt ,  Scott M. Lieberman ,  Stanley G. Nathenson ,  Pere Santamaria ,  Jeffrey Shabanowitz

    发明人： Teresa P. DiLorenzo ,  Anne M. Evans ,  Donald F. Hunt ,  Scott M. Lieberman ,  Stanley G. Nathenson ,  Pere Santamaria ,  Jeffrey Shabanowitz

    IPC分类号： A61K39/00 ,  A61K39/385

    CPC分类号： C07K14/4711

    摘要： The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.

    摘要翻译： 本发明基于负责1型糖尿病的CD8 + T细胞的主要配体的鉴定。 该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白（IGRP）。 鉴定了来自IGRP的几种CD8 + T细胞结合肽，包括含有IGRP序列的氨基酸206-214的肽，其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。 因此，本发明提供包含YLKTN（A / I / L / V）FL（SEQ ID NO：3），FLWSVFWLI（SEQ ID NO：4），（T / A）YY（G / T）FLNFM SEQ ID NO：5），LR（L / V）（F / L）（G / N）IDLL（SEQ ID NO：6），KWCANPDWI（SEQ ID NO：7）和SFCKSASIP（SEQ ID NO：8） 。 还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物，其中寡肽能够结合人MHC I类分子。 此外，提供使用上述组合物治疗哺乳动物的各种方法，其中哺乳动物处于或具有1型糖尿病的风险。 还提供了防止对胰岛细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物和细胞的方法，其中所述方法也使用上述组合物。 还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法，其中所述方法使用上述组合物。