Ifn-gamma-inducible regulatory t cell convertible anti-cancer (irtca) antibody and uses thereof

Abstract

Provided are IFN-γ-Inducible Regulatory T Cell Convertible Anti-Cancer (IRTCA) antibodies and antigen-binding fragment thereof that bind to an activation-inducible TNFR (AITR) polypeptide. Various in vitro and in vivo methods and compositions related to IRTCA antibodies described herein are also provided. Methods include, for example, changing cytokine secretion from T cells in vivo or in vitro and prevention and/or therapeutic treatment of cancer using an IRTCA antibody or fragment thereof.

1 .- 57 . (canceled) 
     
     
         58 . A nucleic acid molecule encoding an IFN-gamma-Inducible Regulatory T Cell Convertible Anti-Cancer (IRTCA) antibody or antigen-binding fragment, comprising:
 a) a heavy chain CDR1 comprising SEQ ID NO: 8, a heavy chain CDR2 comprising SEQ ID NO: 25, and a heavy chain CDR3 comprising SEQ ID NO: 16; and   b) a light chain CDR1 comprising SEQ ID NO: 11, a light chain CDR2 comprising SEQ ID NO: 12, and a light chain CDR3 comprising SEQ ID NO: 18.   
     
     
         59 . The nucleic acid molecule of  claim 58 , wherein the nucleic acid further encodes for heavy chain variable region comprising SEQ ID NO: 20 and light chain variable region comprising SEQ ID NO: 23. 
     
     
         60 . A recombinant vector comprising the nucleic acid molecule of  claim 58 . 
     
     
         61 . A recombinant vector comprising the nucleic acid molecule of  claim 59 . 
     
     
         62 . A host cell comprising the recombinant vector of  claim 60 . 
     
     
         63 . A host cell comprising the recombinant vector of  claim 61 . 
     
     
         64 . The host cell of  claim 62 , wherein the host cell is selected from a bacterial, yeast, insect, or mammalian cell. 
     
     
         65 . The host cell of  claim 64 , wherein the host cell is selected from the group consisting of  E. coli, P. pastoris , Sf9, COS, HEK293, Expi293, CHO-S, CHO-DG44, CHO-K1, and a mammalian lymphocyte. 
     
     
         66 . A nucleic acid molecule encoding an IFN-gamma-Inducible Regulatory T Cell Convertible Anti-Cancer (IRTCA) antibody or antigen-binding fragment, comprising:
 a) a heavy chain CDR1 comprising SEQ ID NO: 24, a heavy chain CDR2 comprising SEQ ID NO: 25, and a heavy chain CDR3 comprising SEQ ID NO: 16; and   b) a light chain CDR1 comprising SEQ ID NO: 11, a light chain CDR2 comprising SEQ ID NO: 12, and a light chain CDR3 comprising SEQ ID NO: 13.   
     
     
         67 . The nucleic acid molecule of  claim 66 , wherein the nucleic acid further encodes for heavy chain variable region comprising SEQ ID NO: 21, and light chain variable region SEQ ID NO: 22. 
     
     
         68 . A recombinant vector comprising the nucleic acid molecule of  claim 66 . 
     
     
         69 . A recombinant vector comprising the nucleic acid molecule of  claim 67 . 
     
     
         70 . A host cell comprising the recombinant vector of  claim 68 . 
     
     
         71 . A host cell comprising the recombinant vector of  claim 69 . 
     
     
         72 . The host cell of  claim 70 , wherein the host cell is selected from a bacterial, yeast, insect, or mammalian cell. 
     
     
         73 . The host cell of  claim 72 , wherein the host cell is selected from the group consisting of  E. coli, P. pastoris , Sf9, COS, HEK293, Expi293, CHO-S, CHO-DG44, CHO-K1, and a mammalian lymphocyte. 
     
     
         74 . A method of inducing an immune response in a subject in need thereof, comprising:
 administering to the subject a composition that comprises or delivers the IRTCA nucleic acid of  claim 58 .   
     
     
         75 . A method of enhancing an immune response or increasing the activity of an immune cell in a subject in need thereof, comprising:
 administering to the subject a composition that comprises or delivers the IRTCA nucleic acid of  claim 58 .   
     
     
         76 . A method of inducing an immune response in a subject in need thereof, comprising:
 administering to the subject a composition that comprises or delivers the IRTCA nucleic acid of  claim 66 .   
     
     
         77 . A method of enhancing an immune response or increasing the activity of an immune cell in a subject in need thereof, comprising:
 administering to the subject a composition that comprises or delivers the IRTCA nucleic acid of  claim 66 .