US2022324963A1PendingUtilityA1

Compositions and methods for treating cancer

72
Assignee: THE TRUSTEES OF THE UNIVERITY OF PENNSYLVANIAPriority: Jan 18, 2011Filed: Nov 17, 2021Published: Oct 13, 2022
Est. expiryJan 18, 2031(~4.5 yrs left)· nominal 20-yr term from priority
Inventors:Daniel J. Powell, Jr.George CoukosMariangela FiginiSilvana Canevari
C07K 2318/20C07K 2317/622C07K 14/7051A61P 35/00C07K 2319/74C07K 16/28C07K 2319/03A61K 2035/124C07K 14/705A61K 39/39558C07K 14/70517A61K 2039/505C12N 15/11C07K 14/70578C07K 2319/02A61P 37/04C07K 2319/30A61K 38/00A61K 39/0011A61K 35/17A61K 2039/5156A61K 2039/5158A61K 40/11A61K 40/31A61K 40/4202A61K 2239/59C12N 5/0636
72
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Claims

Abstract

The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having α-folate receptor (FRα) binding domain and 4-1BB (CD137) costimulatory domain to treat ovarian cancer.

Claims

exact text as granted — not AI-modified
1 . An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the isolated nucleic acid sequence comprises a nucleic acid sequence encoding an α-folate receptor (FRα) antibody comprising the amino acid sequence of SEQ ID NO: 15. 
     
     
         2 . The isolated nucleic acid sequence of  claim 1 , wherein the CAR further comprises a CD3 zeta signaling domain. 
     
     
         3 . The isolated nucleic acid sequence of  claim 2 , wherein the CD3 zeta signaling domain comprises an amino acid sequence of SEQ ID NO: 19. 
     
     
         4 . The isolated nucleic acid sequence of  claim 2 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence of SEQ ID NO: 7. 
     
     
         5 . The isolated nucleic acid sequence of  claim 1 , wherein the CAR further comprises a transmembrane domain. 
     
     
         6 . An isolated chimeric antigen receptor (CAR), wherein the CAR comprises an α-folate receptor (FRα) antibody comprising the amino acid sequence of SEQ ID NO: 15. 
     
     
         7 . The isolated CAR of  claim 6 , wherein the CAR further comprises a CD3 zeta signaling domain. 
     
     
         8 . The isolated CAR of  claim 7 , wherein the CD3 zeta signaling domain comprises an amino acid sequence of SEQ ID NO: 19. 
     
     
         9 . The isolated CAR of  claim 7 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence of SEQ ID NO: 7. 
     
     
         10 . The isolated CAR of  claim 6 , wherein the CAR further comprises a transmembrane domain. 
     
     
         11 . A method for providing anti-tumor immunity in a subject, the method comprising: administering to the subject an effective amount of a T cell comprising the CAR of  claim 6 , thereby providing anti-tumor immunity in the subject. 
     
     
         12 . The method of  claim 11 , wherein the CAR further comprises a 4-1BB costimulatory domain 
     
     
         13 . The method of  claim 12 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18. 
     
     
         14 . The method of  claim 12 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         15 . A method for stimulating a T cell-mediated immune response to a cell population or tissue in a subject, the method comprising: administering to the subject an effective amount of a T cell comprising the CAR of  claim 6 , thereby stimulating a T cell-mediated immune response in the subject. 
     
     
         16 . The method of  claim 15 , wherein the CAR further comprises a 4-1BB costimulatory domain. 
     
     
         17 . The method of  claim 16 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18. 
     
     
         18 . The method of  claim 16 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         19 . A method for treating an ovarian cancer in a subject, the method comprising:
 administering to the subject an effective amount of a T cell comprising the CAR of  claim 6 , thereby treating the ovarian cancer in the subject.   
     
     
         20 . The method of  claim 19 , wherein the CAR further comprises a 4-1BB costimulatory domain 
     
     
         21 . The method of  claim 20 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18. 
     
     
         22 . The method of  claim 20 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         23 . A method for treating cancer in a subject, the method comprising:
 administering to the subject an effective amount of a T cell comprising the CAR of  claim 6 , thereby treating cancer in the subject.   
     
     
         24 . The method of  claim 23 , wherein the CAR further comprises a 4-1BB costimulatory domain 
     
     
         25 . The method of  claim 24 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18. 
     
     
         26 . The method of  claim 24 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         27 . A method of generating a persisting population of genetically engineered T cells in a subject diagnosed with ovarian cancer, the method comprising: administering to the subject an effective amount of a T cell comprising the CAR of  claim 6 , wherein the persisting population of genetically engineered T cells persists in the subject for at least one month after administration. 
     
     
         28 . The method of  claim 27 , wherein the CAR further comprises a 4-1BB costimulatory domain 
     
     
         29 . The method of  claim 28 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18. 
     
     
         30 . The method of  claim 28 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         31 . The isolated nucleic acid sequence of  claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         32 . The isolated nucleic acid sequence of  claim 1 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         33 . The isolated CAR of  claim 6 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         34 . The isolated CAR of  claim 6 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         35 . The method of  claim 11 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         36 . The method of  claim 11 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         37 . The method of  claim 15 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         38 . The method of  claim 15 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         39 . The method of  claim 19 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         40 . The method of  claim 19 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         41 . The method of  claim 23 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         42 . The method of  claim 23 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         43 . The method of  claim 27 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         44 . The method of  claim 27 , wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1.

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