公开(公告)号：US20210070819A1

公开(公告)日：2021-03-11

申请号：US16981352

申请日：2019-03-15

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Universite de Paris ,  Centre National de la Recherche Scientifique (CNRS) ,  Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris ,  Université Libre de Bruxelles

发明人： Roberto MALLONE ,  Joëlle VINH ,  Yann VERDIER ,  Decio LAKS EIZIRIK ,  Maikel Luis COLLI ,  Georgia AFONSO ,  Sergio GONZALEZ-DUQUE

IPC分类号： C07K14/47 ,  C07K14/74 ,  C07K16/18 ,  A61K39/00

摘要： Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (TID), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Secretogranin V (SCG5/7B2) was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative SCG5-009 mRNA splice isoform. Accordingly, the present invention relates to antigenic peptides derived from secretogranin V and uses thereof for the diagnosis and treatment of T1D.

公开(公告)号：US20210023209A1

公开(公告)日：2021-01-28

申请号：US16981462

申请日：2019-03-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITE DE PARIS ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS

发明人： Roberto MALLONE ,  Yann VERDIER ,  Joëlle VINH ,  Marie-Eliane AZOURY ,  Sergio GONZALEZ-DUQUE ,  Georgia AFONSO

IPC分类号： A61K39/395 ,  C07K14/47 ,  C07K14/725 ,  C12N15/115 ,  C12N15/62

摘要： Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. PCSK2 was identified as a novel β-cell antigen, which was processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from PCSK2 and uses thereof for the diagnosis and treatment of T1D.

公开(公告)号：US20210024603A1

公开(公告)日：2021-01-28

申请号：US16981474

申请日：2019-03-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITE DE PARIS ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS

发明人： Roberto MALLONE ,  Sergio GONZALEZ-DUQUE ,  Yann VERDIER ,  Marie-Eliane AZOURY ,  Georgia AFONSO ,  Joëlle VINH

IPC分类号： C07K14/575 ,  C12N15/115 ,  C07K16/26 ,  C07K14/74

摘要： Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naive CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D.

公开(公告)号：US20160341718A1

公开(公告)日：2016-11-24

申请号：US15112475

申请日：2015-01-20

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PARIS - SUD

发明人： Roberto MALLONE ,  Victor APPAY ,  Anna LISSINA

IPC分类号： G01N33/50 ,  A61K39/00 ,  C12N5/0783 ,  C12N5/095 ,  C12N5/0784

CPC分类号： G01N33/505 ,  A61K39/0011 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0695 ,  C12N2500/84 ,  C12N2501/06 ,  C12N2501/22 ,  C12N2501/2301 ,  C12N2501/2304 ,  C12N2501/2307 ,  C12N2501/24 ,  C12N2501/25 ,  C12N2501/999

摘要： The present invention relates to methods for testing T cell priming efficacy in a subject. In particular the present invention relates to an in vitro method for testing T cell priming efficacy in a subject comprising the steps of a) providing sample from the subject, b) culturing the sample in a medium which induces the differentiation of dendritic cells, c) maturing the dendritic cells obtained at step a) in presence of an amount of at least one antigen and an amount of at least one cytokine or ligand suitable for the activation of a pathogen recognition receptor, d) priming and expanding the T cells present in the sample and e) analyzing the func tionality of the primed T cells.

摘要翻译： 本发明涉及在受试者中测试T细胞引发功效的方法。 特别地，本发明涉及一种用于在受试者中测试T细胞引发功效的体外方法，包括以下步骤：a）从受试者提供样品，b）在诱导树突状细胞分化的培养基中培养样品，c） 使步骤a）获得的树突状细胞在至少一种抗原和至少一种适合于激活病原体识别受体的细胞因子或配体的量存在下成熟，d）引发和扩增存在于 样品和e）分析引发T细胞的功能。

公开(公告)号：US20180207250A1

公开(公告)日：2018-07-26

申请号：US15745273

申请日：2016-07-13

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  UNIVERSITE PARIS DESCARTES ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6) ,  UNIVERSITE PARIS DIDEROT - PARIS 7 ,  UNIVERSITÉ PARIS-SUD ,  SORBONNE UNIVERSITE

发明人： Roberto MALLONE ,  Slobodan CULINA ,  Nimesh GUPTA ,  Sebastien LACROIX-DESMAZES

IPC分类号： A61K39/00 ,  A61P37/06

CPC分类号： A61K39/0008 ,  A61K2039/542 ,  A61K2039/577 ,  A61K2039/6056 ,  A61P37/06

摘要： The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

公开(公告)号：US20180244746A1

公开(公告)日：2018-08-30

申请号：US15756091

申请日：2016-09-16

申请人： INSERM (INSTITUTE NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PARIS DESCARTES ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Roberto MALLONE ,  Georgia AFONSO ,  Ana Ines LALANNE ,  Slobodan CULINA

IPC分类号： C07K14/725 ,  C12Q1/6881 ,  C12N15/86 ,  G01N33/566

CPC分类号： C07K14/7051 ,  C07K2319/00 ,  C07K2319/33 ,  C12N15/86 ,  C12Q1/6881 ,  G01N33/566 ,  G01N2333/7051

摘要： The present invention relates to T-cell receptors (TCR) that recognize pancreatic betacell epitopes and uses thereof for the diagnosis and treatment of diabetes.