公开(公告)号：EP0757557A1

公开(公告)日：1997-02-12

申请号：EP95917593.0

申请日：1995-04-25

申请人： THE TRUSTEES OF DARTMOUTH COLLEGE ,  UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

发明人： NOELLE, Randolph J. ,  DURIE, Fiona H. ,  PARKER, David C. ,  APPEL, Michael C. ,  PHILIPS, Nancy E. ,  MORDES, John P. ,  GRENIER, Dale L. ,  ROSSINI, Aldo A.

IPC分类号： C12N15 ,  A61K31 ,  A61K35 ,  A61K38 ,  A61K39 ,  A61P3 ,  A61P37 ,  C07K14 ,  C07K16 ,  C12P21 ,  C12R1

CPC分类号： A61K39/001 ,  A61K35/17 ,  A61K35/39 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/705 ,  C07K16/2875 ,  C07K2317/73 ,  Y10S514/885 ,  A61K2300/00

摘要： Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipient are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.

公开(公告)号：EP0757557B1

公开(公告)日：2005-02-02

申请号：EP95917593.6

申请日：1995-04-25

申请人： THE TRUSTEES OF DARTMOUTH COLLEGE ,  UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

发明人： NOELLE, Randolph J. ,  DURIE, Fiona H. ,  PARKER, David C. ,  APPEL, Michael C. ,  PHILIPS, Nancy E. ,  MORDES, John P. ,  GRENIER, Dale L. ,  ROSSINI, Aldo A.

IPC分类号： A61K39/00

CPC分类号： A61K39/001 ,  A61K35/17 ,  A61K35/39 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/705 ,  C07K16/2875 ,  C07K2317/73 ,  Y10S514/885 ,  A61K2300/00

摘要： Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipient are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.