Abstract: The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity, which comprise a first domain comprising a first antigen variable region which binds to DLL3 and a second domain comprising a second antigen variable region which binds to T cell receptor complex. The present inventors prepared further bispecific antibodies, and assessed their T cell-dependent cell cytotoxicity (TDCC), and found that they also show strong TDCC activity. Since the molecules/antibodies of the present invention show a strong cytotoxicity against cells expressing DLL3, novel pharmaceutical compositions comprising the molecules/antibodies for treating or preventing various cancers associated with DLL3 can be provided.

Abstract: 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.

Abstract: Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Abstract: 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.

Abstract: The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity, which comprise a first domain comprising a first antigen variable region which binds to DLL3 and a second domain comprising a second antigen variable region which binds to T cell receptor complex. The present inventors prepared further bispecific antibodies, and assessed their T cell-dependent cell cytotoxicity (TDCC), and found that they also show strong TDCC activity. Since the molecules/antibodies of the present invention show a strong cytotoxicity against cells expressing DLL3, novel pharmaceutical compositions comprising the molecules/antibodies for treating or preventing various cancers associated with DLL3 can be provided.

Abstract: The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3?, CD3?, and CD3? in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3?, CD3?, and CD3?. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

Abstract: The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.

Abstract: The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity, which comprise a first domain comprising a first antigen variable region which binds to DLL3 and a second domain comprising a second antigen variable region which binds to T cell receptor complex. The present inventors prepared further bispecific antibodies, and assessed their T cell-dependent cell cytotoxicity (TDCC), and found that they also show strong TDCC activity. Since the molecules/antibodies of the present invention show a strong cytotoxicity against cells expressing DLL3, novel pharmaceutical compositions comprising the molecules/antibodies for treating or preventing various cancers associated with DLL3 can be provided.

Abstract: The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.

Abstract: Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Abstract: The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.

Abstract: Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Abstract: The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3?, CD3?, and CD3? in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3?, CD3?, and CD3?. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

Abstract: 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 cells.

Abstract: A method for diagnosing cancer comprising detecting ROBO1 protein is disclosed. In addition, a method for treating a disease caused by abnormal cell growth comprising administrating an antibody that binds to ROBO1, as well as a pharmaceutical composition, a cell growth inhibitor and an anticancer agent comprising an antibody that binds to ROBO1 as an active ingredient are disclosed. Further, a method for inducing cell damages in a ROBO1 expressing cell and a method for inhibiting the growth of a ROBO1 expressing cell by bringing a ROBO1 expressing cell into contact with an antibody that binds to ROBO1, are disclosed. Furthermore, a method for monitoring progression of hepatitis by detecting ROBO1 protein is disclosed.

Abstract: 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.

Abstract: A method for diagnosing cancer comprising detecting ROBO1 protein is disclosed. In addition, a method for treating a disease caused by abnormal cell growth comprising administrating an antibody that binds to ROBO1, as well as a pharmaceutical composition, a cell growth inhibitor and an anticancer agent comprising an antibody that binds to ROBO1 as an active ingredient are disclosed. Further, a method for inducing cell damages in a ROBO1 expressing cell and a method for inhibiting the growth of a ROBO1 expressing cell by bringing a ROBO1 expressing cell into contact with an antibody that binds to ROBO1, are disclosed. Furthermore, a method for monitoring progression of hepatitis by detecting ROBO1 protein is disclosed.

Abstract: An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.

Abstract: 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.

Abstract: A method for diagnosing cancer comprising detecting ROBO1 protein is disclosed. In addition, a method for treating a disease caused by abnormal cell growth comprising administrating an antibody that binds to ROBO1, as well as a pharmaceutical composition, a cell growth inhibitor and an anticancer agent comprising an antibody that binds to ROBO1 as an active ingredient are disclosed. Further, a method for inducing cell damages in a ROBO1 expressing cell and a method for inhibiting the growth of a ROBO1 expressing cell by bringing a ROBO1 expressing cell into contact with an antibody that binds to ROBO1, are disclosed. Furthermore, a method for monitoring progression of hepatitis by detecting ROBO1 protein is disclosed.