Chugai Seiyaku Kabushiki Kaisha

Jichi Medical University

National Institutes of Biomedical Innovation, Health and Nutrition

Genentech, Inc.

University of Miyazaki

Pharmalogicals Research Pte. Ltd.

Atsuhiko Kato

Masami Suzuki

Koichi Matsubara

Shinta Kobayashi

Tatsumi Yamazaki

Hisafumi Okabe

Yu Jau Chen

Ryo Konno

Takeshi Watanabe

Shuji Hayashi

Ayako Kakiuchi

Izumi Yanagisawa

Hidetomo Kitamura

Toru Esaki

Yasuko Kinoshita

Sachiho Netsu

Osamu Natori

Tadashi Sankai

Tomoyuki Igawa

Yoshinori Watanabe

Hiroyuki Tsunoda

Atsuhiko Maeda

Toshihiko Ohtomo

Taichi Kuramochi

Hirotake Shiraiwa

Tatsuhiko Tachibana

Masamichi Sugimoto

Shigero Tamba

Yoshinori Narita

Mika Endo

Keiko Esaki

Hiroaki Kataoka

Hirotake Takai

Chie Kato

Masaki Yamazaki

Kenji Adachi

Etsuko Takeiri

Eri Hashimoto

COMPOSITION FOR PROPHYLAXIS OR TREATMENT OF IL-8 RELATED DISEASES

Provided is a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. A human cancer tissue was repeatedly grown in a NOG mouse, separated cancer cells from the grown cancer tissue, and tested and compared various cancer cell culture processes. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process.

Cancer stem cell population and method for production thereof

An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.

Cancer stem cell-specific molecule

For example, therapeutic methods and the like for novel IL-8-related diseases using an IL-8 signal inhibitor are provided. Alternatively, for example, therapeutic methods and the like for known or novel IL-8-related diseases using a novel anti-IL-8 antibody are provided.

Composition for prophylaxis or treatment of IL-8 related diseases

The invention provides compositions and methods for treating cancers. The methods comprising administering a PD-1 axis binding antagonist and an anti-GPC3 antibody. The compositions comprising a pharmaceutical composition for treating cancer which comprises a PD-1 axis binding antagonist and an anti-GPC3 antibody. Also disclosed are a pharmaceutical composition to be used in combination with a PD-1 axis binding antagonist for treating cancer which comprises an anti-GPC3 antibody as the active ingredient; and a pharmaceutical composition to be used in combination with an anti-GPC3 antibody for treating cancer which comprises as the active ingredient a PD-1 axis binding antagonist.

Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies

An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

Method for searching and screening for target of anti-cancer agent using non-human animal model having NOG established cancer cell line transplanted therein

The purpose of the present invention is to provide: a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. For achieving the purpose, the present inventors grew a human cancer tissue repeatedly in a NOG mouse, separated cancer cells from the grown cancer tissue, and made a comparison of various cancer cell culture processes with each other. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process, and consequently the present invention has been accomplished.

Method for treating IL-8-related diseases

An objective of the present invention is to provide: a cancer stem cell isolated using a cell marker; a substantively homogeneous cancer stem cell population including said cancer stem cell; and a method of preparing said cancer stem cell population. Another objective of the present invention is to provide: a method for separating cancer stem cells with a high proliferative potential and those with a low proliferative potential; a method for inducing cancer stem cells to have a different proliferative potential; and cancer stem cells separated or induced by these separation or induction methods. A further objective of the present invention is to provide: a method of screening for pharmaceuticals using said cancer stem cell or cancer stem cell population; a method for detecting the presence of said cancer stem cell or cancer stem cell population and for identifying or quantifying the same. The present inventors discovered that highly pure colon cancer stem cells (CSC) can be obtained in a large quantity, and identified two types of states of colon CSCs distinguishable through Lgr5 expression.

Cancer stem cell isolation

The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cancer cells.

Humanized anti-epiregulin antibody, and cancer therapeutic agent comprising said antibody as active ingredient

The present invention relates to an in-vitro immunoassay method for detecting the presence of liver cancer cells in a subject. In the method of the present invention, antigen retrieval treatment based on heat-induced epitope retrieval method and antigen retrieval treatment based on protease-induced epitope retrieval method can be combined in the detection of glypican 3 antigen expression in liver cancer tissues to thereby detect the difference in the expression level or expression pattern of the glypican 3 antigen by immunohistochemical staining method. This enables samples, which has been determined by the conventional HIER method as highly expressing glypican 3, to be graded according to the expression level of glypican 3.

Method for detection of liver cancer cell using anti-glypican-3 antibody

Chondrogenesis promoters and indolin-2-one derivatives

Chondrongenesis promotors and indolin-2-one derivatives

Growing community of inventors

Shizuoka, Japan

Atsuhiko Kato