Compositions and Methods for Treating Cancer with TSLPR-CD19 or TSLPR-CD22 Immunotherapy

Abstract

Chimeric antigen receptors containing TSLPR-CD19 and TSLPR-CD22 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

1 . An isolated nucleic acid molecule encoding a TSLPR-CD19 tandem chimeric antigen receptor (CAR) or a TSLPR-CD22 CAR comprising at least one extracellular antigen binding domain comprising either a TSLPR-CD19 antigen binding domain or a TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the TSLPR-CD19 tandem CAR or TSLPR-CD22 CAR is encoded by a nucleotide sequence comprising SEQ ID NO. 84, 86, 88, 90, 96, or 98. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . The isolated nucleic acid molecule of  claim 1 , wherein the nucleic acid sequence encoding the TSLPR-CD19 tandem CAR or TSLPR-CD22 tandem CAR is encoded by a nucleotide sequence comprising SEQ ID NO. 84, 86, 88, 90, 96, or 98 or a sequence with 85%, 90%, 95%, 96%, 97%, 98% or 99% identity thereof. 
     
     
         10 . The isolated nucleic acid molecule of  claim 1 , wherein the encoded at least one intracellular signaling domain further comprises a CD3 zeta intracellular domain 
     
     
         11 .- 13 . (canceled) 
     
     
         14 . A chimeric antigen receptor (CAR) encoded by the isolated nucleic acid molecule of  claim 1 . 
     
     
         15 - 23 . (canceled) 
     
     
         24 . A vector comprising a nucleic acid molecule of  claim 1 . 
     
     
         25 . The vector of  claim 24 , wherein the vector is selected from the group consisting of a DNA vector, an RNA vector, a plasmid vector, a cosmid vector, a herpes virus vector, a measles virus vector, a lentivirus vector, an adenoviral vector, or a retrovirus vector, or a combination thereof. 
     
     
         26 - 27 . (canceled) 
     
     
         28 . An isolated cell comprising the vector of  claim 24 . 
     
     
         29 - 31 . (canceled) 
     
     
         32 . A method of making a cell comprising transducing a T cell with a vector of  claim 24 . 
     
     
         33 . A method of generating a population of RNA-engineered cells comprising introducing an in vitro transcribed RNA or synthetic RNA into a cell, wherein the RNA comprises a nucleic acid molecule encoding a TSLPR-CD19 tandem chimeric antigen receptor (CAR) or a TSLPR-CD22 CAR comprising at least one extracellular antigen binding domain comprising either a TSLPR-CD19 antigen binding domain or a TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the TSLPR-CD19 tandem CAR or TSLPR-CD22 CAR is encoded by a nucleotide sequence comprising SEQ ID NO. 84, 86, 88, 90, 96, or 98. 
     
     
         34 - 35 . (canceled) 
     
     
         36 . A pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the population of human T cells comprise a nucleic acid sequence that encodes a tandem chimeric antigen receptor (CAR), wherein the CAR comprises at least one extracellular antigen binding domain comprising a TSLPR-CD19 antigen binding domain or a TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the tandem CAR comprises an amino acid sequence comprising SEQ ID NO: 85, 87, 89, 91, 97, or 99 and wherein the population of human T cells are T cells of a human having a cancer. 
     
     
         37 - 48 . (canceled)