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1. WO2000041724 - MODULATION OF SYSTEMIC MEMORY T CELL TRAFFICKING

Publication Number WO/2000/041724
Publication Date 20.07.2000
International Application No. PCT/US2000/000953
International Filing Date 14.01.2000
Chapter 2 Demand Filed 10.08.2000
IPC
A61K 38/19 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
19Cytokines; Lymphokines; Interferons
C07K 16/24 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
24against cytokines, lymphokines or interferons
C07K 16/28 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
CPC
A61K 2039/505
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
505comprising antibodies
A61K 38/195
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
19Cytokines; Lymphokines; Interferons
195Chemokines, e.g. RANTES
A61P 17/02
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
17Drugs for dermatological disorders
02for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 17/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
17Drugs for dermatological disorders
06Antipsoriatics
A61P 19/02
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
19Drugs for skeletal disorders
02for joint disorders, e.g. arthritis, arthrosis
C07K 16/24
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
24against cytokines, lymphokines or interferons
Applicants
  • THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY [US/US]; Suite 350 900 Welch Road Palo Alto, CA 94304, US
  • MILLENNIUM PHARMACEUTICALS, INC. [US/US]; 75 Sidney Street Cambridge, MA 02139, US
Inventors
  • BUTCHER, Eugene, C.; US
  • CAMPBELL, James, J.; US
  • WU, Lijun; US
  • ROTTMAN, James, B.; US
Agents
  • SHERWOOD, Pamela, J.; Bozicevic, Field & Francis LLP Suite 200 200 Middlefield Road Menlo Park, CA 94025, US
Priority Data
09/232,87815.01.1999US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) MODULATION OF SYSTEMIC MEMORY T CELL TRAFFICKING
(FR) MODULATION DU TRAFIC DES LYMPHOCYTES T A MEMOIRE DE LA CIRCULATION SYSTEMIQUE
Abstract
(EN)
methods are provided to specifically modulate the trafficking of systemic memory T cells, particularly CD4+ T cells, without affecting naive T cells or intestinal memory T cells. It is shown that systemic memory T cells, which are characterized as CD45Ra-, and integrin $g(a)4$g(b)7-, express high levels of CCR4. Ligands or CCR4, such as TARC or MDC, act as an adhesion trigger, wherein upon CCR4 binding, these cells undergo integrin-dependent arrest to the appropriate vascular receptor(s). This arrest acts to localize the cells at the target site. The methods of the invention manipulate this triggering, and CCR4 mediated chemotaxis, to affect the localization of T cells in targeted tissues. In one embodiment of the invention, the active agent is a CCR4 agonist, that acts to enhance T cell localization. In an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity. An advantage of the invention is the selectivity for systemic memory T cells, without affecting native T cells or intestinal memory T cells.
(FR)
L'invention concerne des méthodes de modulation spécifique du trafic des lymphocytes T à mémoire de la circulation systémique, notamment les lymphocytes T CD4+, sans affecter les lymphocytes T naifs ou les lymphocytes T à mémoire intestinaux. Les lymphocytes T à mémoire de la circulation systémique, dénommés CD45Ra-, et l'intégrine $g(a)4$g(b)7- expriment des niveaux élevés de CCR4. Les ligands de CCR4, tels que TARC ou MDC, servent de déclencheur d'adhérence : après leur liaison avec CCR4, ces cellules subissent un arrêt dépendant de l'intégrine au niveau des récepteurs vasculaires appropriés. Cet arrêt permet de localiser les cellules au niveau du site cible. Les méthodes selon l'invention permettent de manipuler ce déclenchement, ainsi que la chimiotaxie médiée par CCR4, pour agir sur la localisation des lymphocytes T dans des tissus cible. Selon un mode de réalisation de l'invention, l'agent actif est un agoniste de CCR4 qui permet d'améliorer la localisation des lymphocytes T. Selon un autre mode de réalisation, l'agent est un antagoniste qui bloque l'activité biologique de CCR4. Les méthodes selon l'invention sont avantageuses en ce qu'elles visent sélectivement les lymphocytes T à mémoire de la circulation systémique, sans avoir d'effets sur les lymphocytes T natifs ou les lymphocytes T à mémoire intestinaux.
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