公开(公告)号：EP3552628A1

公开(公告)日：2019-10-16

申请号：EP19161747.1

申请日：2013-09-09

申请人： The Trustees Of Dartmouth College ,  King's College London

发明人： NOELLE, Randolph J.

IPC分类号： A61K39/395 ,  A61K48/00 ,  A61P35/00

摘要： The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring "checkpoint" protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

公开(公告)号：EP3421486A1

公开(公告)日：2019-01-02

申请号：EP18173447.6

申请日：2013-06-21

申请人： The Trustees Of Dartmouth College ,  King's College London

发明人： NOELLE, Randolph J. ,  CEERAZ, Sabrina ,  LEMERCIER, Isabelle ,  NOWAK, Elizabeth ,  LINES, Janet Louise

IPC分类号： C07K14/47 ,  C07K16/28 ,  C07K19/00 ,  A61K39/00 ,  A61P35/00 ,  A61P37/00 ,  A01K67/027 ,  A61K38/17 ,  C07K14/705 ,  C12N15/113

摘要： The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V- domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig), preferably also containing a flexible linker intervening the VISTA and Ig Fc polypeptide. The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions, especially lupus, multiple sclerosis, psoriasis, psoriatic arthritis, multiple sclerosis, Crohn's disease, inflammatory bowel disease and type 1 or type 2 diabetes.

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.

公开(公告)号：EP3267969A1

公开(公告)日：2018-01-17

申请号：EP16762355.2

申请日：2016-03-08

申请人： King's College London

发明人： NOELLE, Randolph J. ,  LORD, Graham M ,  BROWN, Chrysothemis C

IPC分类号： A61K8/49 ,  A61K8/67 ,  A61K31/07 ,  A61K31/203 ,  A61P35/00

CPC分类号： A61K39/39 ,  A61K31/196 ,  A61K31/203 ,  A61K31/428 ,  A61K31/69 ,  A61K35/17 ,  A61K39/0011 ,  A61K39/39558 ,  A61K45/06 ,  A61K2035/124 ,  A61K2039/55511 ,  A61K2039/57

摘要： Encompassed are methods of potentiating anti-tumor immunity comprising administering an RARα agonist to a patient having a tumor in combination with at least one other treatment and methods of suppressing a Th17 response in a patient comprising administering an RARα agonist in combination with at least one other treatment.