COMPOSITION AND METHOD FOR MODULATING DENDRITIC CELL-T CELL INTERACTION

• Main Authors: TEUNIS BERNARD HERMAN GEIJTENBEEK, YVETTE VAN KOOYK, CARL GUSTAV FIGDOR, RUURD TORENSMA
• Format: Patent
• Language: English; Portuguese
• Published: 25.08.2010
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TESTING; VINEGAR; WINE

Use of a compound (I) that binds to a C-type lectin (II) on the surface of a dendritic cell (DC) for producing a composition for modulating (especially reducing) the immune response in an animal (particularly human or other mammal), provided that (II) is not the DEC-205 receptor. Independent claims are also included for the following: (1) an antibody (Ab), preferably monoclonal, directed against a C-type lectin (IIa) having a fully defined sequence of about 400 amino acids (given in the specification) or its natural variants, equivalents, parts, fragments or epitopes; (2) a pharmaceutical composition containing Ab and at least one carrier, excipient, adjuvant or auxiliary; (3) a combination of (I) attached to an antigen (Ag) or its fragment; (4) a method for producing, isolating and/or purifying DC from a biological sample or culture medium; and (5) DC prepared by method in (4). ACTIVITY : Immunosuppressant; immunostimulant; anti-allergic; antiviral; antitumor; antibacterial; antiprotozoal. MECHANISM OF ACTION : (I) mediates adhesion between DC and other cells by inhibiting interaction between (II) and (i) an ICAM (intracellular adhesion molecule) on T cells or (ii) gp 120 on HIV (human immune deficiency virus)-infected cells. A new (II), DC-SIGN, is not only involved in DC-T cell clumping but is also a major HIV receptor. Cells of the leukemia line K562 were transfected to express ICAM-3 and tested for binding to DC. Clumping between the cells was inhibited by antibodies directed against DC-SIGN, and DC-mediated T cell proliferation was then only about 1/3 of that in an antibody-free medium. The effect was greatly increased when anti-LFA3 antibodies were additionally present (practically no proliferation).