Administration of kynurenine depleting enzymes for tumor therapy

Abstract

Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

1 .- 51 . (canceled) 
     
     
         52 . A method of treating a subject having a tumor comprising administering to the subject an effective amount of a T cell expressing a kynureninase. 
     
     
         53 . The method of  claim 52 , wherein the kynureninase is a modified kynureninase. 
     
     
         54 . The method of  claim 53 , wherein the modified kynureninase comprises an amino acid sequence at least 90% identical to any of SEQ ID NOs: 8 and 10-12. 
     
     
         55 . The method of  claim 53 , wherein the modified kynureninase comprises a Phe306Met substitution or a Phe306Leu substitution. 
     
     
         56 . The method of  claim 52 , wherein the T cell expresses a T cell receptor. 
     
     
         57 . The method of  claim 52 , wherein the T cell express a chimeric antigen T cell receptor (CAR). 
     
     
         58 . The method of  claim 57 , wherein the CAR is targeted to a cancer cell antigen. 
     
     
         59 . The method of  claim 52 , wherein the kynureninase comprises a heterologous peptide segment. 
     
     
         60 . The method of  claim 59 , wherein the heterologous peptide segment is an XTEN peptide, an IgG Fc, an albumin, or an albumin binding peptide. 
     
     
         61 . A T cell expressing a transgene encoding a kynureninase. 
     
     
         62 . The T cell of  claim 61 , wherein the kynureninase comprises an amino acid sequence at least 90% identical to any of SEQ ID NOs: 8 and 10-12. 
     
     
         63 . The T cell of  claim 62 , wherein the kynureninase is a modified kynureninase. 
     
     
         64 . The T cell of  claim 63 , wherein the modified kynureninase comprises a Phe306Met substitution or a Phe306Leu substitution. 
     
     
         65 . The T cell of  claim 61  wherein the T cell expresses a T cell receptor. 
     
     
         66 . The T cell of  claim 61 , wherein the T cell expresses a CAR. 
     
     
         67 . The T cell of  claim 66 , wherein the CAR is targeted to a cancer cell antigen.