IP Library › Granted Patent US 12,721,890
Granted Patent B2
US 12,721,890 · App. 18/024,557 · Granted Sep 1, 2026

T cell receptors recognizing R273C or Y220C mutations in P53

Inventors: Sanghyun Kim (Rockville, MD); Nikolaos Zacharakis (Gaithersburg, MD); Steven A. Rosenberg (Potomac, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
A61K40/11A61K40/32A61K40/4241C07K14/7051C12N5/0636C12N15/86A61K40/50C07K2319/50C12N2501/2302C12N2740/10043
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Quick Facts
Patent No.
US 12,721,890
App. No.
18/024,557
Granted
Sep 1, 2026
Kind
B2
Abstract

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53 R273C or human p53 Y220C . Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Claims (19)

1 . An isolated or purified nucleic acid comprising a nucleotide sequence encoding a T cell receptor (TCR) having antigenic specificity for a human p53 R273C amino acid sequence, wherein the TCR comprises the amino acid sequences of

all of SEQ ID NOs: 59-64.

2 . An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises the amino acid sequences of all of SEQ ID NOs: 59-64.

3 . An isolated or purified nucleic acid comprising a nucleotide sequence encoding a protein comprising a first polypeptide chain comprising the amino acid sequences of all of SEQ ID NOs: 59-61 and a second polypeptide chain comprising the amino acid sequences of all of SEQ ID NOs: 62-64.

4 . An isolated or purified nucleic acid comprising, from 5′ to 3′, a first nucleotide sequence and a second nucleotide sequence, wherein the first and second nucleotide sequence, respectively, encode the amino sequences of SEQ ID NOs: 65 and 66; 66 and 65; 67 and 68; 68 and 67; 69 and 70; 70 and 69; 69 and 68; 68 and 69; 133 and 70; 70 and 133; 133 and 134; 134 and 133; 65 and 132; 132 and 65; 131 and 66; 66 and 131; 131 and 132; 132 and 131; 71 and 72; 72 and 71; 73 and 74; 74 and 73; 75 and 76; or 76 and 75.

5 . The isolated or purified nucleic acid of claim 4 , further comprising a third nucleotide sequence interposed between the first and second nucleotide sequence, wherein the third nucleotide sequence encodes a cleavable linker peptide.

6 . The isolated or purified nucleic acid of claim 5 , wherein the cleavable linker peptide comprises the amino acid sequence of

(SEQ ID NO: 100)

RAKRSGSGATNFSLLKQAGDVEENPGP.

7 . The isolated or purified nucleic acid of claim 6 , which encodes an amino acid sequence of SEQ ID NO: 77.

8 . A recombinant expression vector comprising the nucleic acid of claim 1 .

9 . The recombinant expression vector of claim 8 , which is a transposon or a lentiviral vector.

10 . A method of producing a host cell expressing a TCR that has antigenic specificity for the peptide of SGNLLGRNSFEVCVCACPGRDRRTE (SEQ ID NO: 117), the method comprising contacting a cell with the vector of claim 8 under conditions that allow introduction of the vector into the cell.

11 . An isolated or purified host cell comprising the nucleic acid of claim 1 .

12 . The host cell of claim 11 , wherein the cell is a human lymphocyte.

13 . The host cell of claim 11 , wherein the cell is selected from the group consisting of a T cell, a natural killer T (NKT) cell, an invariant natural killer T (iNKT) cell, and a natural killer (NK) cell.

14 . An isolated or purified population of cells comprising the host cell of claim 11 .

15 . A method of producing a TCR, the method comprising culturing the host cell of claim 11 so that the TCR is produced.

16 . A pharmaceutical composition comprising (a) the population of cells of claim 14 and (b) a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 25, 2023
From: KIM, SANGHYUN; ZACHARAKIS, NIKOLAOS; ROSENBERG, STEVEN A.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 063434/0182 →
Continuity (2)
Provisional Application 63074747 · Sep 4, 2020
Related Publication 20230321240A1 · Oct 12, 2023
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