公开(公告)号：US06464978B1

公开(公告)日：2002-10-15

申请号：US08055006

申请日：1993-04-29

申请人： Steven W. Brostoff ,  Darcy B. Wilson ,  Lawrence R. Smith ,  Daniel P. Gold ,  Dennis J. Carlo

发明人： Steven W. Brostoff ,  Darcy B. Wilson ,  Lawrence R. Smith ,  Daniel P. Gold ,  Dennis J. Carlo

IPC分类号： A61K39395

CPC分类号： G01N33/564 ,  A61K39/00 ,  A61K2039/53 ,  C07K14/7051 ,  G01N33/56972 ,  G01N2800/102 ,  G01N2800/285

摘要： The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. The vaccine is administered to the mammal in a manner that induces an immunologically effective response so as to affect the course of the disease. The invention additionally provides specific &bgr;-chain variable regions of the T cell receptor, designated V&bgr;6.2/3, V&bgr;6.5, V&bgr;2, V&bgr;5.1, V&bgr;13 and V&bgr;7, which are central to the pathogenesis of multiple sclerosis (MS).

摘要翻译： 本发明提供疫苗和疫苗接种哺乳动物的手段，以便预防或控制特定的T细胞介导的病理学或治疗T细胞的未调节复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 以诱导免疫有效应答以影响疾病进程的方式向哺乳动物施用疫苗。 本发明另外提供T细胞受体的特异性β链可变区，称为Vbet6.2 / 3，Vbeta6.5，Vbeta2，Vbeta5.1，Vbeta13和Vbeta7，它们是多发性硬化（MS）发病机制的核心。

公开(公告)号：US06413516B1

公开(公告)日：2002-07-02

申请号：US08182967

申请日：1994-01-14

申请人： Jennie C. C. Chang ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Jennie C. C. Chang ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K3900

CPC分类号： A61K39/0008 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/2809 ,  C07K16/4258 ,  G01N33/56972 ,  G01N2800/285

摘要： This invention relates to methods of preventing or reducing the severity of psoriasis. In one embodiment, the method involves administering to the individual a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor, present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells. In particular, the T cell receptor has the V&bgr; region-V&bgr;3, V&bgr;13.1 or V&bgr;17. In another embodiment, the method involves gene therapy. The invention also relates to methods of diagnosing psoriasis by determining the presence of psoriasis predominant T cell receptors.

摘要翻译： 本发明涉及预防或减轻银屑病严重程度的方法。 在一个实施方案中，该方法包括向个体施用存在于介导牛皮癣或其片段的T细胞表面上的基本上具有T细胞受体的非保守区序列的序列的肽，其中所述肽或片段是 能够对免疫系统产生影响来调节T细胞。 特别地，T细胞受体具有Vbeta-Vbeta3，Vbeta13.1或Vbeta17。 在另一个实施方案中，该方法涉及基因治疗。 本发明还涉及通过确定银屑病主要T细胞受体的存在来诊断牛皮癣的方法。

公开(公告)号：US6007815A

公开(公告)日：1999-12-28

申请号：US332428

申请日：1994-10-31

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  A61P37/06 ,  C07K14/725 ,  A61K39/395 ,  C07K16/42

CPC分类号： C07K14/7051 ,  A61K2039/53 ,  A61K39/00

摘要： The present invention provides vaccines and a means of vaccinating a host so as to prevent or control specific T cell mediated pathologies. The vaccine is composed of anti-idiotypic antibodies which are internal images of a segment of the T cell receptor (TCR) present on the surface of the pathogenic T cells. The vaccine is administered to the host in a manner that induces an immune response directed against the TCR of pathologic T cell. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. Means of determining an appropriate amino acid sequence for such a vaccine are also provided.

摘要翻译： 本发明提供疫苗和疫苗接种宿主的方法，以便预防或控制特定的T细胞介导的病理学。 疫苗由抗独特型抗体组成，其是存在于病原性T细胞表面上的T细胞受体（TCR）区段的内部图像。 以诱导针对病理T细胞的TCR的免疫应答的方式将疫苗施用于宿主。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 还提供了确定这种疫苗的适当氨基酸序列的方法。

公开(公告)号：US5837246A

公开(公告)日：1998-11-17

申请号：US376049

申请日：1995-01-20

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  G01N33/564 ,  G01N33/569 ,  A61K38/00

CPC分类号： C07K14/7051 ,  G01N33/564 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  G01N2800/102 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA). Also provided are means to detect, prevent and treat RA.

公开(公告)号：US6090387A

公开(公告)日：2000-07-18

申请号：US472040

申请日：1995-06-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  A61K48/00 ,  C07K14/725 ,  C07K16/28 ,  C07K16/42 ,  C12N15/12 ,  G01N33/569 ,  C07K7/06 ,  C07K14/44

CPC分类号： C07K16/2809 ,  A61K39/0008 ,  C07K14/7051 ,  C07K16/4258 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  A61K48/00 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific .beta.-chain variable regions of T cell receptors, designated V.beta.3, V.beta.4, V.beta.12, V.beta.14 and V.beta.17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合到MHC抗原呈递细胞或超级抗原完成的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供特定的β链可变区T细胞受体，称为Vβ3，Vβ4，Vβ12，Vβ14和Vβ17，其与自身免疫疾病的发病机制相关，例如类风湿性关节炎 （RA）和多发性硬化（MS）。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US5985552A

公开(公告)日：1999-11-16

申请号：US466860

申请日：1995-06-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  A61K48/00 ,  C07K14/725 ,  C07K16/28 ,  C07K16/42 ,  C12N15/12 ,  G01N33/569 ,  C12P19/34 ,  C07H21/04 ,  G01N33/53

CPC分类号： C07K16/2809 ,  A61K39/0008 ,  C07K14/7051 ,  C07K16/4258 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  A61K48/00 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific .beta.-chain variable regions of T cell receptors, designated V.beta.3, V.beta.4, V.beta.12, V.beta.14 and V.beta.17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合到MHC抗原呈递细胞或超级抗原完成的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供特定的β链可变区T细胞受体，称为Vβ3，Vβ4，Vβ12，Vβ14和Vβ17，其与自身免疫疾病的发病机制相关，例如类风湿性关节炎 （RA）和多发性硬化（MS）。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US06221352B1

公开(公告)日：2001-04-24

申请号：US08471209

申请日：1995-06-06

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39395

CPC分类号： G01N33/56972 ,  A61K39/00 ,  A61K39/0008 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/2809 ,  C07K16/4258 ,  G01N2800/285

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合到MHC抗原呈递细胞或超级抗原完成的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供与自身免疫性疾病如类风湿性关节炎（RA）和多发性硬化（MS）的发病机制相关的T细胞受体的特定β链可变区，称为Vbeta3，Vbeta4，Vbeta12，Vbeta14和Vbeta17。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US06207645B1

公开(公告)日：2001-03-27

申请号：US08276776

申请日：1994-07-18

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K4800

CPC分类号： C07K16/2809 ,  A61K39/00 ,  A61K39/0008 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/4258 ,  G01N33/56972 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供疫苗和疫苗接种脊椎动物的方法，以便预防或控制特定的T细胞介导的病症，包括自身免疫疾病和T细胞的不受调节的复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 这样的肽可以结合与MHC抗原呈递细胞或超级抗原复合的常规抗原。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于脊椎动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供与自身免疫性疾病如类风湿性关节炎（RA）和多发性硬化（MS）的发病机制相关的T细胞受体的特定β链可变区，称为Vbeta3，Vbeta4，Vbeta12，Vbeta14和Vbeta17。 还提供了检测，预防和治疗RA和MS的手段。 还提供了将编码可用作本发明的疫苗的多肽的DNA或RNA给予个体的组织细胞的方法。

公开(公告)号：US6159470A

公开(公告)日：2000-12-12

申请号：US464506

申请日：1995-06-05

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  G01N33/564 ,  G01N33/569 ,  A61K39/395

CPC分类号： C07K14/7051 ,  G01N33/564 ,  G01N33/56972 ,  A61K2039/53 ,  A61K39/00 ,  G01N2800/102 ,  G01N2800/285 ,  Y10S530/868

摘要： The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA). Also provided are means to detect, prevent and treat RA.

摘要翻译： 本发明提供疫苗和疫苗接种哺乳动物的手段，以便预防或控制特定的T细胞介导的病理学或治疗T细胞的未调节复制。 疫苗由T细胞受体（TCR）或其对应于存在于介导病理学的T细胞表面上的TCR的片段组成。 疫苗片段可以是对应于介导所述病理学的T细胞特征的TCR序列的肽。 还提供了确定此类疫苗适当氨基酸序列的方法。 疫苗以诱导针对T细胞的TCR介导病理学的免疫应答的方式施用于哺乳动物。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 本发明另外提供了称为Vβ17的T细胞受体的特异性β链可变区，其为类风湿性关节炎（RA）的发病机制的核心。 还提供了检测，预防和治疗RA的手段。

公开(公告)号：US5861164A

公开(公告)日：1999-01-19

申请号：US146454

申请日：1993-11-01

申请人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

发明人： Mark D. Howell ,  Steven W. Brostoff ,  Dennis J. Carlo

IPC分类号： A61K39/00 ,  C07K14/725 ,  A61K38/00

CPC分类号： C07K14/7051 ,  A61K2039/53 ,  A61K39/00

摘要： The present invention provides vaccines and a means vaccinating a host so as to prevent or control specific T cell medicated proliferative diseases. The vaccine is composed of a pharmaceutically acceptable medium and a segment of the T cell receptor (TCR) present on the surface of the T cells mediating the disease. The vaccine is administered to the host in a manner that induces an immune response directed against the TCR of a pathologic T cell. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. Means of determining an appropriate amino acid sequence for such a vaccine are also provided.

摘要翻译： 本发明提供疫苗和接种宿主的方法，以便预防或控制特异性T细胞药物增殖性疾病。 疫苗由存在于介导该疾病的T细胞表面上的T细胞受体（TCR）的药学上可接受的介质和​​片段组成。 以诱导针对病理T细胞的TCR的免疫应答的方式将疫苗施用于宿主。 这种免疫应答下调调节或去除病原性T细胞，从而消除疾病的发病机制。 还提供了确定这种疫苗的适当氨基酸序列的方法。