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1. WO2007143582 - REVERSAL OF THE SUPPRESSIVE FUNCTION OF SPECIFIC T CELLS VIA TOLL-LIKE RECEPTOR 8 SIGNALING

Publication Number WO/2007/143582
Publication Date 13.12.2007
International Application No. PCT/US2007/070264
International Filing Date 01.06.2007
IPC
A01N 43/04 2006.01
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
43Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
02having rings with one or more oxygen or sulfur atoms as the only ring hetero atom
04with one hetero atom
A01N 63/00 2006.01
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
63Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A01N 65/00 2006.01
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
65Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
A61K 38/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
C12N 5/00 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 15/00 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
CPC
A61K 31/7042
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7042Compounds having saccharide radicals and heterocyclic rings
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
C12N 15/115
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
115Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
C12N 15/117
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
117Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
Applicants
  • BAYLOR COLLEGE OF MEDICINE [US]/[US] (AllExceptUS)
  • WANG, Rong-Fu [US]/[US] (UsOnly)
  • PENG, Guangyong [CN]/[US] (UsOnly)
  • WANG, Yicheng [US]/[US] (UsOnly)
Inventors
  • WANG, Rong-Fu
  • PENG, Guangyong
  • WANG, Yicheng
Agents
  • WHITE, Allen, E.
Priority Data
60/811,03705.06.2006US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) REVERSAL OF THE SUPPRESSIVE FUNCTION OF SPECIFIC T CELLS VIA TOLL-LIKE RECEPTOR 8 SIGNALING
(FR) INVERSION DE LA FONCTION SUPRESSIVE DE LYMPHOCYTES T SPÉCIFIQUES PAR LE SIGNAL DU RÉCEPTEUR 8 DE TYPE TOLL
Abstract
(EN)
CD8+ regulatory T (Treg) cells and &ggr;δ Treg cells profoundly suppress host immune responses and thus protect against autoimmune disease while restricting desired immune responses such as antitumor immunity. Synthetic phosphorothioate-protected, guanosine- containing oligonucleotides can directly reverse the suppressive activity of Treg cells without involving dendritic cells. This effect appears to be transduced by signaling through Toll-like receptor (TLR) 8 and engagement of the MyD88 and IRAK4 molecules in Treg cells, in specific embodiments. Stimulation of Treg cells with natural ligands for human TLR8 recapitulated the effect of the synthetic guanosine-containing oligonucleotides.
(FR)
La présente invention concerne des lymphocytes T régulateurs (Treg) CD8+ et des cellules Treg &ggr;δ qui inhibent totalement les réponses immunitaires d'un hôte et protègent ainsi contre une maladie auto-immune tout en restreignant les réponses immunitaires souhaitées telles que l'immunité anti-tumorale. Des oligonucléotides synthétiques contenant de la guanosine et protégés par du phosphorothioate peuvent inverser directement l'activité inhibitrice des lymphocytes Treg sans impliquer de cellules dendritiques. Dans des modes de réalisation spécifiques, cet effet semble être transduit par le signal du récepteur 8 de type Toll (TLR) et la venue des molécules MyD88 et IRAK4 au contact des cellules Treg. La stimulation de cellules Treg au moyen de ligands naturels des TLR8 humaines reprend l'effet des oligonucléotides synthétiques contenant de la guanosine.
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