Cell injury inducing therapeutic drug for use in cancer therapy

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.

1 - 15 . (canceled) 
     
     
         16 . A method for treating cancer, comprising administering an effective amount of a bispecific antibody that comprises an antibody variable region having glypican 3-binding activity and an antibody variable region having CD3-binding activity,
 wherein the cancer is liver cancer, gastric cancer or head & neck cancer,   wherein the antibody variable region having glypican 3-binding activity and the antibody variable region having CD3-binding activity comprise a common light chain variable region, and   wherein
 (a) the antibody variable region having glypican 3-binding activity comprises heavy chain variable region complementarity-determining region (CDR) 1, CDR2, and CDR3 comprising the amino acid sequences of the CDR1, CDR2, and CDR3 regions comprised in SEQ ID NO: 206, respectively; 
 (b) the antibody variable region having CD3-binding activity comprises heavy chain variable region CDR1, CDR2, and CDR3 comprising the amino acid sequences of the CDR1, CDR2, and CDR3 regions comprised in SEQ ID NO: 168, respectively; and 
 (c) the common light chain variable region comprises CDR1, CDR2, and CDR3 comprising the amino acid sequences of the CDR1, CDR2, and CDR3 regions comprised in SEQ ID NO: 223, respectively. 
   
     
     
         17 . The method of  claim 16 , wherein
 (a) the antibody variable region having glypican 3-binding activity comprises a heavy chain variable region comprising a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 206;   (b) the antibody variable region having CD3-binding activity comprises a heavy chain variable region comprising a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 168; and   (c) the common light chain variable region comprises a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 223.   
     
     
         18 . The method of  claim 16 , wherein the bispecific antibody comprises
 (a) an antibody heavy chain comprising a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 385;   (b) an antibody heavy chain comprising a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 402; and   (c) a common light chain comprising a sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 410.   
     
     
         19 . The method of  claim 16 , wherein the bispecific antibody comprises
 (a) an antibody heavy chain comprising the amino acid sequence of SEQ ID NO: 385;   (b) an antibody heavy chain comprising the amino acid sequence of SEQ ID NO: 402; and   (c) a common light chain comprising the amino acid sequence of SEQ ID NO: 410.   
     
     
         20 . The method of  claim 16  further comprising administering an effective amount of another anticancer agent. 
     
     
         21 . The method of  claim 20 , wherein the bispecific antibody is administered simultaneously with said another anticancer agent. 
     
     
         22 . The method of  claim 20 , wherein the bispecific antibody is administered before or after administration of said another anticancer agent. 
     
     
         23 . The method of  claim 20 , wherein said another anticancer agent is a chemotherapeutic agent, a T cell-activating agonist agent, an immune checkpoint inhibitor, or an angiogenic inhibitor. 
     
     
         24 . The method of  claim 23 , wherein said another anticancer agent is a chemotherapeutic agent, wherein the chemotherapeutic agent is an antimetabolite, a plant alkaloid, or a platinum compound. 
     
     
         25 . The method of  claim 24 , wherein the antimetabolite is capecitabine, the plant alkaloid is paclitaxel, and the platinum compound is cisplatin. 
     
     
         26 . The method of  claim 23 , wherein said another anticancer agent is an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an anti-PD1 antibody, an anti-PDL1 antibody, an anti-CTLA-4 antibody, an anti-TIM3 antibody, or an anti-LAG3 antibody. 
     
     
         27 . The method of  claim 23 , wherein said another anticancer agent is bevacizumab. 
     
     
         28 . The method of  claim 16 , wherein the cancer is liver cancer. 
     
     
         29 . The method of  claim 17 , wherein the cancer is liver cancer. 
     
     
         30 . The method of  claim 19 , wherein the cancer is liver cancer. 
     
     
         31 . The method of  claim 20 , wherein the cancer is liver cancer. 
     
     
         32 . The method of  claim 16 , wherein the cancer is gastric cancer. 
     
     
         33 . The method of  claim 16 , wherein the cancer is head & neck cancer. 
     
     
         34 . A method for treating cancer, comprising administering an effective amount of an antibody that binds CD3. 
     
     
         35 . A method for treating cancer, comprising administering an effective amount of an antibody that binds glypican 3.