Astellas Pharma Gmbh

National Cancer Center

Fumiko Chiwaki

Hiroki Sasaki

Masayuki Komatsu

Yoshiyuki Tenda

Masatoshi Yuri

Takeshi Tsutsumi

Daisuke Yamajuku

Yuko Kusuzaki

Shigenori Yagi

Hiroki Shirai

Kazunori Hirayama

Yoshiki Satake

An objective of the present invention is to provide an anti-TSPAN8/anti-CD3 bispecific antibody and an anti-TSPAN8 antibody usable in treatment or prevention in human. A human monoclonal antibody producing mouse was immunized with a peritoneal disseminated cancer cell isolated from a patient, to obtain an antibody 16B11 and an antibody 16B12 that selectively bind to a peritoneal disseminated cancer cell. These antibodies were anti-TSPAN8 antibodies that bind to the region from amino acid positions 126 to 155 of TSPAN8 and exhibited strong binding activity to TSPAN8 expressed in the peritoneal disseminated cancer cell. Further, an anti-TSPAN8(16B11)-anti-CD3 bispecific antibody produced based on the sequence of 16B11 exhibited a cytotoxic activity against the TSPAN8-expressing cancer cell in vitro, exerted an anti-tumor action on TSPAN8-expressing cancer cell-bearing mice in vivo, and extended the lifetime of peritoneal dissemination model mice.

Anti-TSPAN8/anti-CD3 bispecific antibody and anti-TSPAN8 antibody

An object of the present invention is to provide an anti-CLDN4/anti-CD137 bispecific antibody usable in treatment of cancer. An anti-CLDN4/anti-CD137 bispecific antibody produced using an anti-CLDN4 antibody binding to CLDN4 and an anti-CD137 antibody binding to CD137 had agonistic activity for CD137, promoted production of interferon γ by a T cell, and exhibited cytotoxic activity against a cancer cell expressing CLDN4 on a cell surface thereof. Besides, it was shown that the anti-CLDN4/anti-CD137 bispecific antibody can be safely administered to monkeys. Therefore, the anti-CLDN4/anti-CD137 bispecific antibody is usable in treatment of human cancer.

Anti-CLDN4/anti-CD137 bispecific antibody

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Chuo-ku, Japan

Fumiko Chiwaki