IP Library Granted Patent US 10,544,392
Granted Patent B2
US 10,544,392 · App. 15/567,157 · Granted Jan 28, 2020

Methods of isolating T cells and T cell receptors having antigenic specificity for a cancer-specific mutation from peripheral blood

Inventors: Alena Gros (Washington, DC); Steven A. Rosenberg (Potomac, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
C12N5/0636A61K38/1703A61P35/00C12N15/63
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Quick Facts
Patent No.
US 10,544,392
App. No.
15/567,157
Granted
Jan 28, 2020
Kind
B2
Abstract

Disclosed are methods of isolating T cells and TCRs having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.

Claims (52)

1. An isolated or purified nucleic acid comprising a nucleotide sequence encoding a TCR, or an antigen-binding portion thereof, wherein the TCR, and the antigen-binding portion thereof, comprise the amino acid sequences of:

(a) SEQ ID NOs: 5-10 or

(b) SEQ ID NOs: 13-18.

2. The nucleic acid according to claim 1 , wherein the TCR, and the antigen-binding portion thereof, comprise the amino acid sequences of:

(a) SEQ ID NOs: 11-12 or

(b) SEQ ID NOs: 19-20.

3. The nucleic acid according to claim 1 , wherein the TCR, and the antigen-binding portion thereof, further comprise the amino acid sequences of:

(a) SEQ ID NO: 45, wherein

(i) X at position 48 is Thr or Cys;

(ii) X at position 112 is Ser, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;

(iii) X at position 114 is Met, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(iv) X at position 115 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(b) SEQ ID NO: 46, wherein X at position 57 is Ser or Cys.

4. The nucleic acid according to claim 1 , wherein the TCR, and the antigen-binding portion thereof, comprise the amino acid sequences of:

(a) SEQ ID NOs: 51-52 or

(b) SEQ ID NOs: 53-54.

5. An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises the amino acid sequences of:

(a) SEQ ID NOs: 5-10 or

(b) SEQ ID NOs: 13-18.

6. The nucleic acid according to claim 5 , wherein the polypeptide comprises the amino acid sequence of:

(a) SEQ ID NOs: 11-12 or

(b) SEQ ID NOs: 19-20.

7. The nucleic acid according to claim 5 , wherein the polypeptide further comprises the amino acid sequences of:

(a) SEQ ID NO: 45, wherein

(i) X at position 48 is Thr or Cys;

(ii) X at position 112 is Ser, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;

(iii) X at position 114 is Met, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(iv) X at position 115 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(b) SEQ ID NO: 46, wherein X at position 57 is Ser or Cys.

8. The nucleic acid according to claim 5 , wherein the polypeptide comprises the amino acid sequences of:

(a) SEQ ID NOs: 51-52 or

(b) SEQ ID NOs: 53-54.

9. An isolated or purified nucleic acid comprising a nucleotide sequence encoding a protein, wherein the protein comprises:

(a) a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 5-7 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 8-10 or

(b) a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 13-15 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 16-18.

10. The nucleic acid of claim 9 , wherein the protein comprises:

(a) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 11 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 12 or

(b) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 19 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 20.

11. The nucleic acid of claim 9 , wherein:

(a) the first polypeptide chain further comprises the amino acid sequence of SEQ ID NO: 45, wherein

(i) X at position 48 is Thr or Cys;

(ii) X at position 112 is Ser, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;

(iii) X at position 114 is Met, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(iv) X at position 115 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and

(b) the second polypeptide chain further comprises the amino acid sequence of SEQ ID NO: 46, wherein X at position 57 is Ser or Cys.

12. The nucleic acid according to claim 9 , wherein the protein comprises:

(a) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 51 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 52 or

(b) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 53 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 54.

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

14. A host cell comprising the recombinant expression vector of claim 13 .

15. A population of cells comprising at least one host cell of claim 14 .

16. A pharmaceutical composition comprising the population of cells of claim 15 and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 4, 2018
From: GROS, ALENA; ROSENBERG, STEVEN A.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 044537/0564 →
Continuity (2)
Provisional Application 62155830 · May 1, 2015
Related Publication 20180148690A1 · May 31, 2018
Cited By (10)
US 12,195,507 US 12,195,508 US 12,195,509 US 12,240,877 US 12,240,878 US 12,247,057 US 12,275,768 US 12,281,146 US 12,297,245 US 12,570,760