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1.发明授权MHC class II antigen presenting cells containing oligonucleotides which inhibit Ii protein expression 有权含有抑制Ii蛋白表达的寡核苷酸的MHC II类抗原呈递细胞公开(公告)号：US06368855B1
公开(公告)日：2002-04-09
申请号：US09205995
申请日：1998-12-04
申请人： Minzhen Xu , Gang Qiu , Robert Humphreys
发明人： Minzhen Xu , Gang Qiu , Robert Humphreys
IPC分类号： C12N508
CPC分类号： C12N15/1138 , A61K38/00 , C12N15/113 , C12N2310/111 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3521
摘要： Disclosed is a specific regulator of Ii protein expression or immunoregulatory function. Specifically disclosed are several forms of the specific regulator of Ii, including those which function through the formation of a duplex molecule with an RNA molecule encoding mammalian Ii protein to inhibit Ii protein synthesis at the translation level. This class includes copolymers comprised of nucleotide bases which hybridize specifically to the RNA molecule encoding mammalian Ii protein, and also expressible reverse gene constructs. In other aspects, the disclosure relates to MHC class II-positive antigen presenting cells containing a specific regulator of Ii expression. Such cells are useful, for example, in the display of autodeterminant peptides in association with MHC class II proteins. Compositions of the invention find application in methods for treating diseases, for example malignancies and autoimmune disorders, in a patient by enhancing immunological attack on undesired cells. An additional application is the isolation of autodeterminant peptides from a cell.
摘要翻译： 公开了Ii蛋白表达或免疫调节功能的特异性调节剂。 具体公开的是Ii的特异性调节剂的几种形式，包括通过形成具有编码哺乳动物Ii蛋白的RNA分子的双链体分子起作用以抑制翻译水平的Ii蛋白质合成的那些形式。 该类包括与编码哺乳动物Ii蛋白的RNA分子特异性杂交的核苷酸碱基以及可表达的反向基因构建体的共聚物。 在其他方面，本公开涉及含有Ii表达特异性调节剂的MHC II类阳性抗原呈递细胞。 这样的细胞可用于例如与MHC II类蛋白相关的显示自身决定肽。 本发明的组合物可用于通过增强对不想要的细胞的免疫攻击来治疗患者中的疾病，例如恶性肿瘤和自身免疫性疾病的方法。 另外的应用是从细胞中分离出自身决定肽。
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公开(公告)号：US20070178094A1
公开(公告)日：2007-08-02
申请号：US11732639
申请日：2007-04-04
申请人： Robert Humphreys , Sharlene Adams , Minzhen Xu
发明人： Robert Humphreys , Sharlene Adams , Minzhen Xu
CPC分类号： C07K19/00 , A61K38/00 , C07K14/70539 , G01N33/505
摘要： The present invention provides an MHC class II antigen presentation enhancing hybrid polypeptide. The hybrid has an N-terminus comprising the mammalian Ii key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and modifications thereof which retain antigen presentation enhancing activity, a C-terminus comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, and an intervening chemical structure covalently linking the N-terminal and C-terminal components.
摘要翻译： 本发明提供了增强MHC II类抗原呈递的杂交多肽。 杂合体具有包含哺乳动物Ii关键肽LRMKLPKPPKPVSKMR（SEQ ID NO：1）的N末端及其保留抗原呈递增强活性的修饰，C末端包含多肽形式的抗原表位或肽模拟结构，其结合 涉及MHC II类分子的抗原肽结合位点，以及共价连接N-末端和C-末端组分的中间化学结构。
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公开(公告)号：US20100150953A1
公开(公告)日：2010-06-17
申请号：US12635656
申请日：2009-12-10
申请人： Robert Humphreys , Minzhen Xu
发明人： Robert Humphreys , Minzhen Xu
IPC分类号： A61K39/385 , A61P35/00
CPC分类号： A61K39/0011 , A61K2039/55516 , A61K2039/55522
摘要： Provided are methods and compositions for treating cancer in humans, the cancer being characterized by expression of Her-2/neu. The methods involve vaccinating a patient with an Ii-Key/MHC class II hybrid construct and thereby stimulating an immune response to the native Her-2/neu protein. The construct may be in the form of an Ii-Key hybrid peptide or a nucleic acid encoding an Ii-Key hybrid peptide. Methods are described wherein the cancer being treated is breast cancer. Also claimed is a pharmaceutical composition comprising an Ii-Key/MHC class II hybrid construct with and without an adjuvant. The adjuvant can include GM-CSF. The Ii-Key hybrid construct includes the LRMK residues of Ii-Key protein and an MHC Class II epitope of a protein or portion thereof which is used in the vaccine or a DNA encoding the same hybrid peptide.
摘要翻译： 提供用于治疗人类癌症的方法和组合物，该癌症的特征在于Her-2 / neu的表达。 所述方法涉及用Ii-Key / MHC II类杂交构建体接种患者，从而刺激对天然Her-2 / neu蛋白的免疫应答。 构建体可以是Ii-Key杂交肽或编码Ii-Key杂交肽的核酸的形式。 描述了其中所治疗的癌症是乳腺癌的方法。 还要求保护的是包含具有和不具有佐剂的Ii-Key / MHC II类杂交构建体的药物组合物。 佐剂可以包括GM-CSF。 Ii-Key杂交构建体包括Ii-Key蛋白的LRMK残基和用于疫苗的蛋白质或其部分的MHC II类表位或编码相同杂交肽的DNA。
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公开(公告)号：US20090060936A1
公开(公告)日：2009-03-05
申请号：US12002083
申请日：2007-12-13
申请人： Robert Humphreys , Minzhen Xu
发明人： Robert Humphreys , Minzhen Xu
IPC分类号： A61K39/385 , A61P35/00
CPC分类号： A61K39/0011 , A61K2039/55516 , A61K2039/55522
摘要： Provided are methods and compositions for treating cancer in humans, the cancer being characterized by expression of Her-2/neu. The methods involve vaccinating a patient with an Ii-Key/MHC class II hybrid construct and thereby stimulating an immune response to the native Her-2/neu protein. The construct may be in the form of an Ii-Key hybrid peptide or a nucleic acid encoding an Ii-Key hybrid peptide. Methods are described wherein the cancer being treated is breast cancer. Also claimed is a pharmaceutical composition comprising an Ii-Key/MHC class II hybrid construct with and without an adjuvant. The adjuvant can include GM-CSF. The Ii-Key hybrid construct includes the LRMK (SEQ ID NO: 2) residues of Ii-Key protein and an MHC Class II epitope of a protein or portion thereof which is used in the vaccine or a DNA encoding the same hybrid peptide.
摘要翻译： 提供用于治疗人类癌症的方法和组合物，该癌症的特征在于Her-2 / neu的表达。 所述方法涉及用Ii-Key / MHC II类杂交构建体接种患者，从而刺激对天然Her-2 / neu蛋白的免疫应答。 构建体可以是Ii-Key杂交肽或编码Ii-Key杂交肽的核酸的形式。 描述了其中所治疗的癌症是乳腺癌的方法。 还要求保护的是包含具有和不具有佐剂的Ii-Key / MHC II类杂交构建体的药物组合物。 佐剂可以包括GM-CSF。 Ii-Key杂交构建体包括用于疫苗的蛋白质或其部分的Ii-Key蛋白的LRMK（SEQ ID NO：2）残基和MHC II类表位或编码相同杂交肽的DNA。
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公开(公告)号：US08815249B2
公开(公告)日：2014-08-26
申请号：US12843466
申请日：2010-07-26
申请人： Robert Humphreys , Minzhen Xu
发明人： Robert Humphreys , Minzhen Xu
IPC分类号： A61K39/00 , A61K39/385 , A61K39/145 , A61K48/00 , A61K38/04
CPC分类号： A61K39/385 , A61K39/39 , A61K2039/57 , A61K2039/64
摘要： Disclosed is a nucleic acid molecule comprising a first expressible sequence encoding a protein of interest or polypeptide of interest which contains an MHC Class II-presented epitope, or said encoded protein or peptide. In addition, the nucleic acid molecule comprises a second expressible nucleic acid sequence encoding an antigen presentation enhancing hybrid polypeptide, or said encoded protein or peptide. The antigen presentation enhancing hybrid polypeptide includes the following elements: i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity; ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, the MHC Class II-presented epitope being contained in the protein of interest of step a); and iii) an intervening peptidyl structure linking the N-terminal and C-terminal elements of the hybrid, the peptidyl structure having a length of about 20 amino acids or less.
摘要翻译： 公开了一种核酸分子，其包含编码目标蛋白质或目标多肽的第一可表达序列，其含有MHC II类呈递的表位或所述编码的蛋白质或肽。 此外，核酸分子包含编码抗原呈递增强杂交多肽或所述编码的蛋白质或肽的第二可表达核酸序列。 抗原呈递增强杂交多肽包括以下元件：i）基本上由哺乳动物Ii-Key肽LRMKLPKPPKPVSKMR（SEQ ID NO：1）的4-16个残基组成的N末端元件及其非N末端缺失修饰， 保留抗原呈递增强活性; ii）包含与MHC II类分子的抗原肽结合位点结合的多肽或肽模拟结构形式的MHC II类呈递表位的C末端元件，MHC II类呈递的表位包含在 步骤a）感兴趣的蛋白质; 和iii）连接杂交体的N末端和C末端元件的插入肽基结构，所述肽基结构具有约20个氨基酸或更少的长度。
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公开(公告)号：US20100255019A1
公开(公告)日：2010-10-07
申请号：US12643509
申请日：2009-12-21
CPC分类号： A61K39/0011 , A61K2039/55516 , A61K2039/55522
摘要： Provided are methods and compositions for treating cancer in humans, the cancer being characterized by expression of Her-2/neu. The methods involve vaccinating a patient with an Ii-Key/MHC class II hybrid construct and thereby stimulating an immune response to the native Her-2/neu protein. The construct may be in the form of an Ii-Key hybrid peptide or a nucleic acid encoding an Ii-Key hybrid peptide. Methods are described wherein the cancer being treated is breast cancer. Also claimed is a pharmaceutical composition comprising an Ii-Key/MHC class II hybrid construct with and without an adjuvant. The adjuvant can include GM-CSF. The Ii-Key hybrid construct includes the LRMK [SEQ ID NO.: 2] residues of Ii-Key protein and an MHC Class II epitope of a protein or portion thereof which is used in the vaccine or a DNA encoding the same hybrid peptide.
摘要翻译： 提供用于治疗人类癌症的方法和组合物，该癌症的特征在于Her-2 / neu的表达。 所述方法涉及用Ii-Key / MHC II类杂交构建体接种患者，从而刺激对天然Her-2 / neu蛋白的免疫应答。 构建体可以是Ii-Key杂交肽或编码Ii-Key杂交肽的核酸的形式。 描述了其中所治疗的癌症是乳腺癌的方法。 还要求保护的是包含具有和不具有佐剂的Ii-Key / MHC II类杂交构建体的药物组合物。 佐剂可以包括GM-CSF。 Ii-Key杂交构建体包括用于疫苗的蛋白质或其部分的Ii-Key蛋白的LRMK [SEQ ID NO.:2]残基和MHC II类表位或编码相同杂交肽的DNA。
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公开(公告)号：US09289487B2
公开(公告)日：2016-03-22
申请号：US11033039
申请日：2005-01-11
IPC分类号： A61K39/00 , A61K39/385 , A61K39/39
CPC分类号： A61K39/385 , A61K39/39 , A61K2039/57 , A61K2039/64
摘要： Disclosed is an antigen presentation enhancing hybrid polypeptide which includes three elements. The first element is an N-terminal element consisting essentially of 4-16 residues of the mammalian li-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity. The second element is a chemical structure covalently linking the N-terminal element described above to the MHC Class II-presented epitope described below. The chemical structure is a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of: i) immunologically neutral chemical structures, ii) a MHC Class I epitope or a portion thereof, and/or iii) an antibody-recognized determinant or a portion thereof. Finally, the enhancing antigen presentation enhancing hybrid polypeptide includes a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule.
摘要翻译： 公开了一种抗原呈递增强杂交多肽，其包含三个元件。 第一个元件是基本上由哺乳动物L-钥匙肽LRMKLPKPPKPVSKMR（SEQ ID NO：1）的4-16个残基和保留抗原呈递增强活性的非N末端缺失修饰组成的N末端元件。 第二个元件是共价连接上述N末端元件与下述MHC II类呈递的表位的化学结构。 化学结构是共价连接的原子组，其当以线性方式排列形成柔性链时，其延伸长达20个氨基酸的长度，同样以线性方式排列，所述化学结构选自：i ）免疫中性化学结构，ii）MHC I类表位或其部分，和/或iii）抗体识别的决定簇或其部分。 最后，增强抗原呈递增强的杂合多肽包括C末端元件，其包含多肽或肽模拟结构形式的抗原表位，其结合MHC II类分子的抗原肽结合位点。
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公开(公告)号：US20060008448A1
公开(公告)日：2006-01-12
申请号：US10999208
申请日：2004-11-29
申请人： Minzhen Xu , Robert Humphreys
发明人： Minzhen Xu , Robert Humphreys
IPC分类号： A61K48/00
CPC分类号： C12N15/1138 , A61K38/00 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/111 , C12N2310/14 , C12N2320/10 , C12N2320/30 , C12N2799/022
摘要： The present invention is directed toward compositions and methods involving the inhibition of Ii expression in cells for the purpose of altering antigen presentation pathways. More specifically, disclosed are compositions and methods which relate to MHC Class II molecule presentation of antigenic epitopes which, under normal circumstances, would not be presented in association with MHC Class II molecules. The invention relates to presentation in cells which normally express MHC Class II molecules, as well as cells which can be induced to express MHC Class II molecules. Embodiments relating to RNA interference of Ii are specifically disclosed.
摘要翻译： 本发明涉及包含抑制细胞中Ii表达以改变抗原呈递途径的组合物和方法。 更具体地，公开了涉及抗原表位的MHC II类分子呈递的组合物和方法，其在正常情况下不会与MHC II类分子相关联。 本发明涉及通常表达MHC II类分子的细胞中的表达，以及可以诱导表达MHC II类分子的细胞。 具体公开了与Ii的RNA干扰有关的实施方案。
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公开(公告)号：US08889143B2
公开(公告)日：2014-11-18
申请号：US12635656
申请日：2009-12-10
申请人： Robert Humphreys , Minzhen Xu
发明人： Robert Humphreys , Minzhen Xu
CPC分类号： A61K39/0011 , A61K2039/55516 , A61K2039/55522
摘要： Provided are methods and compositions for treating cancer in humans, the cancer being characterized by expression of Her-2/neu. The methods involve vaccinating a patient with an Ii-Key/MHC class II hybrid construct and thereby stimulating an immune response to the native Her-2/neu protein. The construct may be in the form of an Ii-Key hybrid peptide or a nucleic acid encoding an Ii-Key hybrid peptide. Methods are described wherein the cancer being treated is breast cancer. Also claimed is a pharmaceutical composition comprising an Ii-Key/MHC class II hybrid construct with and without an adjuvant. The adjuvant can include GM-CSF. The Ii-Key hybrid construct includes the LRMK (SEQ ID NO: 2) residues of Ii-Key protein and an MHC Class II epitope of a protein or portion thereof which is used in the vaccine or a DNA encoding the same hybrid peptide.
摘要翻译： 提供用于治疗人类癌症的方法和组合物，该癌症的特征在于Her-2 / neu的表达。 所述方法涉及用Ii-Key / MHC II类杂交构建体接种患者，从而刺激对天然Her-2 / neu蛋白的免疫应答。 构建体可以是Ii-Key杂交肽或编码Ii-Key杂交肽的核酸的形式。 描述了其中所治疗的癌症是乳腺癌的方法。 还要求保护的是包含具有和不具有佐剂的Ii-Key / MHC II类杂交构建体的药物组合物。 佐剂可以包括GM-CSF。 Ii-Key杂交构建体包括Ii-Key蛋白的LRMK（SEQ ID NO：2）残基和用于疫苗的蛋白质或其部分的MHC II类表位或编码相同杂交肽的DNA。
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公开(公告)号：US20100291145A1
公开(公告)日：2010-11-18
申请号：US12843466
申请日：2010-07-26
申请人： Robert Humphreys , Minzhen Xu
发明人： Robert Humphreys , Minzhen Xu
CPC分类号： A61K39/385 , A61K39/39 , A61K2039/57 , A61K2039/64
摘要： Disclosed is a nucleic acid molecule comprising a first expressible sequence encoding a protein of interest or polypeptide of interest which contains an MHC Class II-presented epitope, or said encoded protein or peptide. In addition, the nucleic acid molecule comprises a second expressible nucleic acid sequence encoding an antigen presentation enhancing hybrid polypeptide, or said encoded protein or peptide. The antigen presentation enhancing hybrid polypeptide includes the following elements: i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity; ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, the MHC Class II-presented epitope being contained in the protein of interest of step a); and iii) an intervening peptidyl structure linking the N-terminal and C-terminal elements of the hybrid, the peptidyl structure having a length of about 20 amino acids or less.
摘要翻译： 公开了一种核酸分子，其包含编码目标蛋白质或目标多肽的第一可表达序列，其含有MHC II类呈递的表位或所述编码的蛋白质或肽。 此外，核酸分子包含编码抗原呈递增强杂交多肽或所述编码的蛋白质或肽的第二可表达核酸序列。 抗原呈递增强杂交多肽包括以下元件：i）基本上由哺乳动物Ii-Key肽LRMKLPKPPKPVSKMR（SEQ ID NO：1）的4-16个残基组成的N末端元件及其非N末端缺失修饰， 保留抗原呈递增强活性; ii）包含与MHC II类分子的抗原肽结合位点结合的多肽或肽模拟结构形式的MHC II类呈递表位的C末端元件，MHC II类呈递的表位包含在 步骤a）感兴趣的蛋白质; 和iii）连接杂交体的N末端和C末端元件的插入肽基结构，所述肽基结构具有约20个氨基酸或更少的长度。
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