Immunotherapy with binding agents

Abstract

Binding agents that modulate the immune response are disclosed. The binding agents may include soluble receptors, polypeptides, and/or antibodies. Also disclosed are methods of using the binding agents for the treatment of diseases such as cancer.

1 - 96 . (canceled) 
     
     
         97 . A method of increasing an immune response in a subject comprising: administering to the subject a therapeutically effective amount of a soluble receptor comprising a PVR variant, wherein the soluble receptor:
 (i) inhibits the interaction between TIGIT and PVR;   (ii) inhibits the interaction between CD96 and PVR;   (iii) inhibits the interaction between TIGIT and PVR and inhibits the interaction between CD96 and PVR; or   (iv) inhibits the interaction between TIGIT and PVR, inhibits the interaction between CD96 and PVR, and does not inhibit the interaction between CD226 and PVR.   
     
     
         98 . A method of inhibiting tumor growth in a subject comprising: administering to the subject a therapeutically effective amount of a soluble receptor comprising a PVR variant, wherein the soluble receptor:
 (i) inhibits the interaction between TIGIT and PVR;   (ii) inhibits the interaction between CD96 and PVR;   (iii) inhibits the interaction between TIGIT and PVR and inhibits the interaction between CD96 and PVR; or   (iv) inhibits the interaction between TIGIT and PVR, inhibits the interaction between CD96 and PVR, and does not inhibit the interaction between CD226 and PVR.   
     
     
         99 . The method of  claim 97 , wherein the PVR variant comprises the amino acid sequence of wild-type PVR (SEQ ID NO:1), except for one or more amino acid substitutions of amino acid residues selected from the group consisting of 65, 67, 72, 73, 74, 81, 82, 84, and 85 of wild-type PVR (SEQ ID NO:1). 
     
     
         100 . The method of  claim 98 , wherein the PVR variant comprises the amino acid sequence of wild-type PVR (SEQ ID NO:1), except for one or more amino acid substitutions of amino acid residues selected from the group consisting of 65, 67, 72, 73, 74, 81, 82, 84, and 85 of wild-type PVR (SEQ ID NO:1). 
     
     
         101 . The method of  claim 99 , wherein the one or more amino acid substitutions within the PVR variant comprise substitutions in one or more amino acids:
 (a) corresponding to amino acid 72 of wild-type PVR (SEQ ID NO:1);   (b) corresponding to amino acid 82 of wild-type PVR (SEQ ID NO:1); or   (c) corresponding to amino acid 72 and amino acid 82 of wild-type PVR (SEQ ID NO:1).   
     
     
         102 . The method of  claim 100 , wherein the one or more amino acid substitutions within the PVR variant comprise substitutions in one or more amino acids:
 (a) corresponding to amino acid 72 of wild-type PVR (SEQ ID NO:1);   (b) corresponding to amino acid 82 of wild-type PVR (SEQ ID NO:1); or   (c) corresponding to amino acid 72 and amino acid 82 of wild-type PVR (SEQ ID NO:1).   
     
     
         103 . The method of  claim 99 , wherein the PVR variant comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. 
     
     
         104 . The method of  claim 100 , wherein the PVR variant comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. 
     
     
         105 . The method of  claim 97 , wherein the immune response is directed to a tumor cell or cancer. 
     
     
         106 . The method of  claim 97 , further comprising the administration of at least one additional therapeutic agent. 
     
     
         107 . The method of  claim 106 , wherein the additional therapeutic agent is an immune response stimulating agent, a chemotherapeutic agent, a small molecule agent, and/or an antibody. 
     
     
         108 . The method of  claim 107 , wherein the additional therapeutic agent is an immune response stimulating agent comprising an antibody that blocks immunosuppressive functions. 
     
     
         109 . The method of  claim 98 , further comprising the administration of at least one additional therapeutic agent. 
     
     
         110 . The method of  claim 109 , wherein the additional therapeutic agent is an immune response stimulating agent, a chemotherapeutic agent, a small molecule agent, and/or an antibody. 
     
     
         111 . The method of  claim 110 , wherein the additional therapeutic agent is an immune response stimulating agent comprising an antibody that blocks immunosuppressive functions. 
     
     
         112 . A cell comprising or producing a polypeptide, wherein the polypeptide comprises a poliovirus receptor (PVR) variant, wherein the PVR variant comprises the amino acid sequence of wild-type PVR (SEQ ID NO:1), except for one or more amino acid substitutions of amino acid residues selected from the group consisting of 65, 67, 72, 73, 74, 81, 82, 84, and 85 of wild-type PVR (SEQ ID NO:1). 
     
     
         113 . A polynucleotide encoding the polypeptide produced by the cell of  claim 112 . 
     
     
         114 . A vector comprising the polynucleotide of  claim 113 . 
     
     
         115 . A kit comprising the polynucleotide of  claim 113 .