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1. WO2018067991 - MODULATION OF NOVEL IMMUNE CHECKPOINT TARGETS

Publication Number WO/2018/067991
Publication Date 12.04.2018
International Application No. PCT/US2017/055625
International Filing Date 06.10.2017
IPC
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
51
Preparations containing radioactive substances for use in therapy or testing in vivo
02
characterised by the carrier
04
Organic compounds
08
Peptides, e.g. proteins
10
Antibodies or immunoglobulins; Fragments thereof
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
14
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435
from animals; from humans
705
Receptors; Cell surface antigens; Cell surface determinants
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53
Immunoassay; Biospecific binding assay; Materials therefor
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53
Immunoassay; Biospecific binding assay; Materials therefor
574
for cancer
[IPC code unknown for A61K 47/68]
A61K 51/10 (2006.01)
C07K 14/705 (2006.01)
G01N 33/53 (2006.01)
G01N 33/574 (2006.01)
A61K 47/68 (2017.01)
CPC
A61K 35/17
A61K 45/06
A61K 47/68
C07K 14/70503
C07K 14/7051
C07K 2319/02
Applicants
  • THE BRIGHAM AND WOMEN'S HOSPITAL, INC. [US/US]; 75 Francis Street Boston, Massachusetts 02115, US
  • THE BROAD INSTITUTE, INC. [US/US]; 415 Main Street Cambridge, Massachusetts 02142, US
  • MASSACHUSETTS INSTITUTE OF TECHNOLOGY [US/US]; 77 Massachusetts Avenue Cambridge, Massachusetts 02139, US
  • KUCHROO, Vijay K. [IN/US]; US
  • ANDERSON, Ana Carrizosa [US/US]; US
  • MADI, Asaf [US/US]; US
  • CHIHARA, Norio [US/US]; US
  • REGEV, Aviv [US/US]; US
  • SINGER, Meromit [US/US]; US
  • ZHANG, Huiyuan [CN/US]; US
Inventors
  • KUCHROO, Vijay K.; US
  • ANDERSON, Ana Carrizosa; US
  • MADI, Asaf; US
  • CHIHARA, Norio; US
  • REGEV, Aviv; US
  • SINGER, Meromit; US
  • ZHANG, Huiyuan; US
Agents
  • TALAPATRA, Sunit; US
  • YAN, Tianran; US
  • SCHORR, Kristel; US
  • BERKOWITZ, Benjamin A.; US
  • BECK, George C.; US
  • AGARWAL, Pavan K.; US
  • BRINCKERHOFF, Courtenay; US
  • MAEBIUS, Stephen B.; US
  • SIMKIN, Michele M.; US
Priority Data
62/405,83507.10.2016US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) MODULATION OF NOVEL IMMUNE CHECKPOINT TARGETS
(FR) MODULATION DE NOUVELLES CIBLES DE POINTS DE CONTRÔLE IMMUNITAIRES
Abstract
(EN)
Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co- inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network and novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdml and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the expression of co- inhibitory receptors such as ILT-3 in dysfunctional T cells and identifies novel regulators of T cell dysfunction.
(FR)
Des lymphocytes T dysfonctionnels ou épuisés apparaissent dans des maladies chroniques, notamment les infections virales chroniques et le cancer, et expriment des niveaux élevés de récepteurs co-inhibiteurs. Le blocage thérapeutique de ces récepteurs présente une efficacité clinique dans le traitement du cancer. Tandis que les récepteurs co-inhibiteurs sont co-exprimés, les déclencheurs qui les induisent et les régulateurs transcriptionnels qui entraînent leur co-expression n'ont pas été identifiés. La cytokine IL-27 immunorégulatrice induit un module génique dans des lymphocytes T qui comprend plusieurs récepteurs co-inhibiteurs connus (Tim-3, Lag-3 et TIGIT). La présente invention concerne un nouveau réseau immunorégulateur ainsi que de nouvelles molécules de surface de cellules qui ont une fonction inhibitrice dans le micro-environnement tumoral. La présente invention concerne en outre la nouvelle découverte selon laquelle les facteurs de transcription Prdml et c-Maf régulent coopérativement l'expression du module de récepteurs co-inhibiteurs. Ce circuit moléculaire critique est sous-jacent à l'expression des récepteurs co-inhibiteurs tels que ILT-3 dans les lymphocytes T dysfonctionnels et identifie de nouveaux régulateurs du dysfonctionnement des lymphocytes T.
Also published as
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