Anti-tnfrsf25 antibodies

Abstract

Anti-TNFRSF25 antibodies and variants thereof, including those that bind to an epitope in the region of amino acids 48-71, are disclosed. Also contemplated are uses of the antibodies in research, diagnostic, and therapeutic applications.

1 - 19 . (canceled) 
     
     
         20 . A method of treating a tumor in a subject, comprising administering to a subject an anti-tumor necrosis factor superfamily receptor 25 (TNFRSF25) antibody or antigen binding fragment thereof, wherein the antibody or antibody fragment comprises:
 (a) a heavy chain, the heavy chain comprising:
 (i) a heavy chain variable region comprising, CDR1, CDR2, and CDR3 sequences, wherein the CDR1 sequence is GFTFSNHDLN (SEQ ID NO: 12), the CDR2 sequence is YISSASGLISYADAVRG (SEQ ID NO: 14); and the CDR3 sequence is DPAYTGLYALDF (SEQ ID NO: 26) or DPPYSGLYALDF (SEQ ID NO: 16); and 
   (b) a light chain, the light chain comprising:
 (ii) a light chain variable region comprising, CDR1, CDR2, and CDR3 sequences, wherein the CDR1 sequence is TLSSELSWYTIV (SEQ ID NO: 25), the CDR2 sequence is LKSDGSHSKGD (SEQ ID NO: 21), and the CDR3 sequence is CGAGYTLAGQYGWV (SEQ ID NO: 23). 
   
     
     
         21 . The method of  claim 20 , wherein the heavy chain variable region comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 5. 
     
     
         22 . The method of  claim 20 , wherein the light chain variable region comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 6. 
     
     
         23 . The method of  claim 20 , wherein the heavy chain variable region comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 5, and the light chain variable region comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 6. 
     
     
         24 . The method of  claim 20 , wherein the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 5. 
     
     
         25 . The method of  claim 20 , wherein the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 6. 
     
     
         26 . The method of  claim 20 , wherein the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 5, and the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 6. 
     
     
         27 . The method of  claim 20 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 5. 
     
     
         28 . The method of  claim 20 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 6. 
     
     
         29 . The method of  claim 20 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 5, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 6. 
     
     
         30 . The method of  claim 20 , wherein the heavy constant region of the antibody is selected from human IgG1, IgG2, IgG3, and IgG4. 
     
     
         31 . The method of  claim 30 , wherein the heavy constant region is IgG4. 
     
     
         32 . The method of  claim 20 , wherein the method comprises inducing apoptosis of TNIFRSF25-expressing tumor cells in the tumor. 
     
     
         33 . The method of  claim 20 , wherein the method comprises stimulating proliferation of CD8+ T cells in the subject. 
     
     
         34 . The method of  claim 20 , wherein the method comprises stimulating proliferation of CD4+FoxP3+ regulatory T cells in the subject. 
     
     
         35 . The method of  claim 20 , comprising administering at least one additional agent for treating cancer. 
     
     
         36 . The method of  claim 35 , wherein the at least one additional agent is an agent that targets CTLA-4, PD-1, PD-L1, LAG-3, Tim-3, TNFRSF4, TNFRSF9, TNFRSF18, CD27, CD39, CD47, CD73, or CD278, or is an A2A receptor antagonist or a TGF-beta antagonist. 
     
     
         37 . The method of  claim 35 , wherein the at least one additional agent is a B7 family costimulatory molecule, a TNF receptor superfamily costimulatory molecule, a vaccine composition, or a chemotherapeutic agent. 
     
     
         38 . The method of  claim 35 , wherein the at least one additional agent comprises chimeric antigen receptor-transfected T cells or expanded tumor infiltrating lymphocytes for use in an adoptive T cell therapy in vitro or in a subject.