Methods for treatment of cancer comprising tigit-binding agents

Abstract

Methods for enhancing the immune response and/or treatment of diseases such as cancer comprising an agent that specifically binds TIGIT are disclosed. The TIGIT-binding agents may include polypeptides, antibodies, and/or bispecific agents.

1 - 51 . (canceled) 
     
     
         52 . A method of treating cancer in a human patient having cancer, comprising administering to said human patient a therapeutically effective amount of a full-length antibody that specifically binds the extracellular domain of human TIGIT,
 wherein said human patient is characterized by one or more of the following parts a) through d):   a) was previously treated with a human PD-1 antagonist or a human PD-L1 antagonist and there is tumor growth, progression, or recurrence during or after treatment with said human PD-1 antagonist or said human PD-L1 antagonist; b) has a cancer selected from the group consisting of head and neck cancer, cervical carcinoma, gastric cancer, ovarian cancer, melanoma, sarcoma, lung cancer, gastroesophageal, leukemia, lymphoma, anal cancer, pancreatic cancer, hepatocellular cancer, liver cancer, renal cell carcinoma, kidney cancer, bladder cancer, a microsatellite instability-high colorectal cancer, a microsatellite stable colorectal cancer, a triple negative breast cancer, a Merkel cell carcinoma, an endometrial cancer, and an esophageal cancer; c) has a cancer that expresses poliovirus receptor (PVR) or poliovirus receptor-related 2 (PVRL2); and d) has a cancer that comprises tumor-infiltrating lymphocytes (TILS) or regulatory T-cells; and   wherein said full-length antibody that binds human TIGIT is capable of mediating antibody-dependent cell cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) and comprises a heavy chain CDR1 comprising TSDYAWN (SEQ ID NO:4), a heavy chain CDR2 comprising YISYSGSTSYNPSLRS (SEQ ID NO:5), a heavy chain CDR3 comprising ARRQVGLGFAY (SEQ ID NO:6), a light chain CDR1 comprising KASQDVSTAVA (SEQ ID NO:7), a light chain CDR2 comprising SASYRYT (SEQ ID NO:8), and a light chain CDR3 comprising QQHYSTP (SEQ ID NO:9), and   wherein said full-length antibody that binds human TIGIT is administered at a dose of 1 mg/kg to 80 mg/kg of body weight.   
     
     
         53 . The method of  claim 52 , wherein said full-length antibody that binds human TIGIT comprises:
 (i) a heavy chain variable region comprising SEQ ID NO:10 and a light chain variable region comprising SEQ ID NO:11;   (ii) a heavy chain amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence of SEQ ID NO:15; or   (iii) a heavy chain amino acid sequence of SEQ ID NO:17 and a light chain amino acid sequence of SEQ ID NO:15.   
     
     
         54 . The method of  claim 53 , wherein said full-length antibody that binds human TIGIT comprises:
 (i) a heavy chain variable region comprising SEQ ID NO:10 and a light chain variable region comprising SEQ ID NO:11; or   (ii) a heavy chain amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence of SEQ ID NO:15.   
     
     
         55 . The method of  claim 54 , wherein said full-length antibody that binds human TIGIT comprises a heavy chain amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence of SEQ ID NO:15. 
     
     
         56 . The method of  claim 52 , wherein the method further comprises administering to said patient an additional human therapeutic agent, wherein said additional human therapeutic agent is administered prior to, concurrently with, or subsequently to the administration of said full-length antibody that binds to human TIGIT. 
     
     
         57 . The method of  claim 56 , wherein said additional human therapeutic agent is selected from the group consisting of a human anti-PD-1 antibody and a human anti-PD-L1 antibody. 
     
     
         58 . The method of  claim 57 , wherein said additional human therapeutic is a human anti-PD-1 antibody and is selected from the group consisting of nivolumab, pembrolizumab, and pidilzumab. 
     
     
         59 . The method of  claim 57 , wherein said additional human therapeutic is a human anti-PD-L1 antibody and is selected from the group consisting of atezolizumab, durvalumab, and avelumab. 
     
     
         60 . The method of  claim 52 , wherein said full-length antibody that binds human TIGIT is intravenously administered to said human patient. 
     
     
         61 . The method of  claim 52 , wherein said full-length antibody that binds human TIGIT is administered once every week, once every two weeks, once every three weeks, or once every four weeks. 
     
     
         62 . The method of  claim 52 , wherein said human patient was previously treated with a human PD-1 antagonist or a human PD-L1 antagonist and there is tumor growth, progression, or recurrence during or after treatment with said human PD-1 antagonist or said human PD-L1 antagonist. 
     
     
         63 . The method of  claim 52 , wherein said patient has a cancer selected from the group consisting of head and neck cancer, cervical carcinoma, gastric cancer, ovarian cancer, melanoma, sarcoma, lung cancer, gastroesophageal, leukemia, lymphoma, anal cancer, pancreatic cancer, hepatocellular cancer, liver cancer, renal cell carcinoma, kidney cancer, bladder cancer, a microsatellite instability-high colorectal cancer, a microsatellite stable colorectal cancer, a triple negative breast cancer, a Merkel cell carcinoma, an endometrial cancer, and an esophageal cancer. 
     
     
         64 . The method of  claim 52 , wherein said patient has a cancer that expresses poliovirus receptor (PVR) or poliovirus receptor-related 2 (PVRL2). 
     
     
         65 . The method of  claim 52 , wherein said patient has a cancer that comprises tumor-infiltrating lymphocytes (TILS) or regulatory T-cells. 
     
     
         66 . The method of  claim 57 , wherein said full-length antibody that binds human TIGIT comprises a heavy chain amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence of SEQ ID NO:15; and
 wherein said full-length antibody that binds human TIGIT is intravenously administered to said human patient once every two weeks.   
     
     
         67 . The method of  claim 66 , wherein a human anti-PD-1 antibody is administered prior to, concurrently with, or subsequently to the administration of said antibody that binds to human TIGIT and wherein said human anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilzumab. 
     
     
         68 . The method of  claim 66 , wherein a human anti-PD-L1 antibody is administered prior to, concurrently with, or subsequently to the administration of said antibody that binds to human TIGIT and wherein said human anti-PD-L1 antibody is selected from the group consisting of atezolizumab, durvalumab, and avelumab. 
     
     
         69 . The method of  claim 63 , wherein said full-length antibody that binds human TIGIT comprises a heavy chain amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence of SEQ ID NO:15; and
 wherein said full-length antibody that binds human TIGIT is intravenously administered to said human patient once every two weeks.   
     
     
         70 . The method of  claim 69 , wherein a human anti-PD-1 antibody is administered prior to, concurrently with, or subsequently to the administration of said antibody that binds to human TIGIT and wherein said human anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilzumab. 
     
     
         71 . The method of  claim 69 , wherein a human anti-PD-L1 antibody is administered prior to, concurrently with, or subsequently to the administration of said antibody that binds to human TIGIT and wherein said human anti-PD-L1 antibody is selected from the group consisting of atezolizumab, durvalumab, and avelumab.