ANTI-TSPAN8-ANTI-CD3 BISPECIFIC ANTIBODY AND ANTI-TSPAN8 ANTIBODY

The present invention addresses the problem of providing an anti-TSPAN8-anti-CD3 bispecific antibody and an anti-TSPAN8 antibody each of which can be used for treatment or prevention in human bodies.ã¿¿A human-monoclonal-antibody-producing mouse is immunized with a cancer peritoneal dissemination ce...

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Hauptverfasser:	YURI Masatoshi, KOMATSU Masayuki, YAMAJUKU Daisuke, KUSUZAKI Yuko, TENDA Yoshiyuki, CHIWAKI Fumiko, TSUTSUMI Takeshi, SASAKI Hiroki
Format:	Patent
Sprache:	eng ; spa
Schlagworte:	BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING ORGANIC CHEMISTRY PEPTIDES PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS SPIRITS VINEGAR WINE
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Beschreibung
Zusammenfassung:	The present invention addresses the problem of providing an anti-TSPAN8-anti-CD3 bispecific antibody and an anti-TSPAN8 antibody each of which can be used for treatment or prevention in human bodies.ã¿¿A human-monoclonal-antibody-producing mouse is immunized with a cancer peritoneal dissemination cell isolated from a patient to produce a 16B11 antibody and a 16B12 antibody each of which has been bound selectively to the cancer peritoneal dissemination cell. These antibodies are anti-TSPAN8 antibodies capable of binding to a region lying between amino acid residue Nos. 126 to 155 in TSPAN8, and exhibit a potent binding activity to TSPAN8 expressed in a cancer peritoneal dissemination cell.ã¿¿Furthermore, an anti-TSPAN8(16B11)-anti-CD3 bispecific antibody which is produced on the basis of the sequence for 16B11 shows cytotoxicity to a TSPAN8-expressing cancer cell in vitro, and shows an anti-tumor activity to a cancer-affected mouse carrying a TSPAN8-expressing cancer cell and extends the survival period of a peritoneal dissemination model mouse in vivo. Un objetivo de la presente invención es proporcionar un anticuerpo biespecífico anti-TSPAN8/anti-CD3 y un anticuerpo anti-TSPAN8 utilizable en el tratamiento o prevención en un ser humano. Se inmunizó un ratón productor de anticuerpos monoclonales humanos con una célula cancerosa diseminada peritoneal aislada de un paciente, para obtener un anticuerpo 16B11 y un anticuerpo 16B12 que se unen selectivamente a una célula cancerosa diseminada peritoneal. Estos anticuerpos eran anticuerpos anti-TSPAN8 que se unen a la región de las posiciones de aminoácidos 126 a 155 de TSPAN8 y mostraron una fuerte actividad de unión a TSPAN8 expresada en la célula cancerosa diseminada peritoneal. Además, un anticuerpo biespecífico anti-TSPAN8 (16B11)-anti-CD3 producido sobre la base de la secuencia de 16B11 exhibió una actividad citotóxica contra la célula cancerosa que expresa TSPAN8 in vitro, ejerció una acción antitumoral en ratones portadores de células cancerosas que expresan TSPAN in vivo, y prolongaron la vida útil de los ratones modelo de diseminación peritoneal.