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NZ732045B2 - Anti-mutated kras t cell receptors - Google Patents
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NZ732045B2 - Anti-mutated kras t cell receptors - Google Patents

Anti-mutated kras t cell receptors

Info

Publication number
NZ732045B2
NZ732045B2 NZ732045A NZ73204515A NZ732045B2 NZ 732045 B2 NZ732045 B2 NZ 732045B2 NZ 732045 A NZ732045 A NZ 732045A NZ 73204515 A NZ73204515 A NZ 73204515A NZ 732045 B2 NZ732045 B2 NZ 732045B2
Authority
NZ
New Zealand
Prior art keywords
seq
amino acid
acid sequence
chain
nos
Prior art date
Application number
NZ732045A
Other versions
NZ732045A (en
Inventor
Qiong J Wang
James C Yang
Zhiya Yu
Original Assignee
The United States Of America As Represented By The Secretary Department Of Health And Human Services
Filing date
Publication date
Application filed by The United States Of America As Represented By The Secretary Department Of Health And Human Services filed Critical The United States Of America As Represented By The Secretary Department Of Health And Human Services
Priority claimed from PCT/US2015/062269 external-priority patent/WO2016085904A1/en
Publication of NZ732045A publication Critical patent/NZ732045A/en
Publication of NZ732045B2 publication Critical patent/NZ732045B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/54—Pancreas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • A61K39/001154—Enzymes
    • A61K39/001164—GTPases, e.g. Ras or Rho
    • A61K39/461—
    • A61K39/4632—
    • A61K39/464464—
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/82—Translation products from oncogenes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y306/00—Hydrolases acting on acid anhydrides (3.6)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N33/5748—

Abstract

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for an HLA-A11-restricted epitope of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) (KRAS7-16), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), or Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS). 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 (22)

CLAIMS:
1. An isolated or purified T cell receptor (TCR) having antigenic icity for a mutated epitope presented in the t of an HLA-A11 molecule, the mutated epitope (a) comprising VVVGADGVGK (SEQ ID NO: 2) or (b) consisting of VVVGAVGVGK (SEQ ID NO: 33) or VVGAVGVGK (SEQ ID NO: 35) , wherein the TCR comprises: (a) an a chain complementarity determining region (CDR) 1 sing the amino acid sequence of SEQ ID NO: 3, an a chain CDR2 comprising the amino acid sequence of SEQ ID NO: 4, an a chain CDR3 comprising the amino acid sequence of SEQ ID NO: 5, a ß chain CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a ß chain CDR2 comprising the amino acid ce of SEQ ID NO: 7, and a ß chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8; (b) an a chain CDR 1 comprising the amino acid sequence of SEQ ID NO: 125, an a chain CDR2 comprising the amino acid sequence of SEQ ID NO: 126, an a chain CDR3 comprising the amino acid sequence of SEQ ID NO: 127, a ß chain CDR1 sing the amino acid sequence of SEQ ID NO: 128, a ß chain CDR2 comprising the amino acid sequence of SEQ ID NO: 129, and a ß chain CDR3 comprising the amino acid sequence of SEQ ID NO: 130; (c) an a chain CDR 1 comprising the amino acid sequence of SEQ ID NO: 137, an a chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, an a chain CDR3 comprising the amino acid sequence of SEQ ID NO: 139, a ß chain CDR1 sing the amino acid sequence of SEQ ID NO: 140, a ß chain CDR2 comprising the amino acid sequence of SEQ ID NO: 141, and a ß chain CDR3 sing the amino acid sequence of SEQ ID NO: 142; (d) an a chain CDR 1 comprising the amino acid sequence of SEQ ID NO: 149, an a chain CDR2 comprising the amino acid sequence of SEQ ID NO: 150, an a chain CDR3 comprising the amino acid sequence of SEQ ID NO: 151, a ß chain CDR1 comprising the amino acid sequence of SEQ ID NO: 152, a ß chain CDR2 comprising the amino acid sequence of SEQ ID NO: 153, and a ß chain CDR3 comprising the amino acid sequence of SEQ ID NO: 154; or (e) an a chain CDR1 comprising the amino acid sequence of SEQ ID NO: 149, an a chain CDR2 comprising the amino acid sequence of SEQ ID NO: 150, an a chain CDR3 comprising the amino acid sequence of SEQ ID NO: 207, a ß chain CDR1 comprising the amino acid sequence of SEQ ID NO: 152, a ß chain CDR2 comprising the amino acid sequence of SEQ ID NO: 153, and a ß chain CDR3 comprising the amino acid sequence of SEQ ID NO: 154.
2. The ed or ed TCR of claim 1, comprising: (a) an a chain variable region comprising the amino acid sequence of SEQ ID NO: 9 and a ß chain variable region comprising the amino acid sequence of SEQ ID NO: 10; (b) an a chain variable region comprising the amino acid sequence of SEQ ID NO: 131 and a ß chain variable region comprising the amino acid ce of SEQ ID NO: 132; (c) an a chain variable region comprising the amino acid sequence of SEQ ID NO: 143 and a ß chain le region comprising the amino acid sequence of SEQ ID NO: 144; (d) an a chain variable region sing the amino acid sequence of SEQ ID NO: 155 and a ß chain variable region comprising the amino acid ce of SEQ ID NO: 156; (e) an a chain variable region comprising the amino acid sequence of SEQ ID NO: 208 and a ß chain variable region comprising the amino acid ce of SEQ ID NO: 156.
3. The isolated or purified TCR of claim 1 or 2, further comprising: (a) an a chain constant region comprising the amino acid sequence of SEQ ID NO: 13 and a ß chain constant region comprising the amino acid sequence of SEQ ID NO: 14; (b) an a chain constant region comprising the amino acid sequence of SEQ ID NO: 135 and a ß chain constant region comprising the amino acid sequence of SEQ ID NO: 136; (c) an a chain constant region comprising the amino acid sequence of SEQ ID NO: 147 and a ß chain constant region comprising the amino acid sequence of SEQ ID NO: 148; (d) an a chain constant region comprising the amino acid sequence of SEQ ID NO: 159 and a ß chain constant region comprising the amino acid sequence of SEQ ID NO: 160.
4. The isolated or purified TCR of any one of claims 1-3, comprising: (a) an a chain comprising the amino acid sequence of SEQ ID NO: 11 and a ß chain comprising the amino acid sequence of SEQ ID NO: 12; (b) an a chain comprising the amino acid sequence of SEQ ID NO: 133 and a ß chain comprising the amino acid sequence of SEQ ID NO: 134; (c) an a chain comprising the amino acid sequence of SEQ ID NO: 145 and a ß chain comprising the amino acid sequence of SEQ ID NO: 146; (d) an a chain comprising the amino acid sequence of SEQ ID NO: 157 and a ß chain comprising the amino acid ce of SEQ ID NO: 158; or (e) an a chain comprising the amino acid sequence of SEQ ID NO: 209 and a ß chain comprising the amino acid sequence of SEQ ID NO: 158.
5. The TCR of any one of claims 1-4, having antigenic specificity for the mutated epitope comprising VVVGADGVGK (SEQ ID NO: 2).
6. The TCR of any one of claims 1-4, having antigenic specificity for the mutated e consisting of VVVGAVGVGK (SEQ ID NO: 33) or VVGAVGVGK (SEQ ID NO:
7. An isolated or purified polypeptide comprising a functional portion of the TCR of any one of claims 1-4, wherein the functional portion comprises: (i) the amino acid sequences of SEQ ID NOs: 3-8; (ii) the amino acid sequences of SEQ ID NOs: 0; (iii) the amino acid sequences of SEQ ID NOs: 137-142; (iv) the amino acid sequences of SEQ ID NOs: 149-154; or (v) the amino acid sequences of SEQ ID NOs: 149-150, 207, and 152-154.
8. An isolated or purified polypeptide comprising a functional portion of the TCR of any one of claims 1-4, wherein the functional portion comprises: (i) the amino acid sequence of both SEQ ID NOs: 9 and 10; (ii) the amino acid ce of both SEQ ID NOs: 131 and 132; (iii) the amino acid sequence of both SEQ ID NOs: 143 and 144; (iv) the amino acid sequence of both SEQ ID NOs: 155 and 156; or (v) the amino acid ce of both SEQ ID NOs: 208 and 156.
9. An isolated or purified polypeptide comprising a functional portion of the TCR of any one of claims 1-4, wherein the functional n ses: (i) the amino acid sequence of both SEQ ID NOs: 11 and 12; (ii) the amino acid sequence of both SEQ ID NOs: 133 and 134; (iii) the amino acid sequence of both SEQ ID NOs: 145 and 146; (iv) the amino acid sequence of both SEQ ID NOs: 157 and 158; or (v) the amino acid ce of both SEQ ID NOs: 209 and 158.
10. An isolated or purified protein comprising: (a) a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 3- 5 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 6-8; (b) a first ptide chain comprising the amino acid sequences of SEQ ID NOs: 125-127 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 128-130; (c) a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 9 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 140-142; (d) a first ptide chain comprising the amino acid sequences of SEQ ID NOs: 149-151 and a second polypeptide chain sing the amino acid sequences of SEQ ID NOs: 152-154; or (e) a first polypeptide chain sing the amino acid sequences of SEQ ID NOs: 149, 150, and 207 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 152-154.
11. The isolated or purified protein according to claim 10, comprising: (a) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 9 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 10; (b) a first polypeptide chain sing the amino acid sequence of SEQ ID NO: 131 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 132; (c) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 143 and a second polypeptide chain sing the amino acid sequence of SEQ ID NO: 144; (d) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 155 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 156; or (e) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 208 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 156.
12. The isolated or purified protein of claim 10 or 11, comprising: (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; (b) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 133 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 134; (c) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 145 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 146; (d) a first ptide chain sing the amino acid sequence of SEQ ID NO: 157 and a second polypeptide chain sing the amino acid sequence of SEQ ID NO: 158; or (e) a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 209 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 158.
13. An isolated or purified nucleic acid comprising a tide ce encoding the TCR according to any one of claims 1-6, the polypeptide ing to any one of claims 7-9, or the n according to any one of claims 10-12.
14. A recombinant expression vector comprising the nucleic acid according to claim
15. An isolated host cell comprising the inant expression vector of claim 14.
16. The host cell according to claim 15, wherein the cell is human.
17. A population of cells comprising at least one host cell of claim 15 or 16.
18. A pharmaceutical composition comprising the TCR according to any one of claims 1-6, the polypeptide according to any one of claims 7-9, the protein according to any one of claims 10-12, the nucleic acid according to claim 13, the recombinant expression vector of claim 14, the host cell of claim 15 or 16, or the population of cells of claim 17, and a pharmaceutically acceptable carrier.
19. Use of the host cell of claim 15 or 16 or the population of cells of claim 17, in the manufacture of a medicament for the detection, treatment or prevention of cancer in a human.
20. A method of detecting the presence of cancer in a mammal, the method comprising contacting a sample comprising one or more cells from the mammal with the host cell of claim 15 or 16 or the population of cells of claim 17 thereby forming a complex, and ing the complex, wherein ion of the complex is indicative of the presence of cancer in the mammal.
21. The use of claim 19, or the method of claim 20, wherein the cancer is pancreatic, colorectal, lung, endometrial, ovarian, or prostate cancer.
22. The method of claim 20 or 21, n the sample comprises whole cells, lysates thereof, or a fraction of the whole cell lysates.
NZ732045A 2015-11-24 Anti-mutated kras t cell receptors NZ732045B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462084654P 2014-11-26 2014-11-26
US201562171321P 2015-06-05 2015-06-05
PCT/US2015/062269 WO2016085904A1 (en) 2014-11-26 2015-11-24 Anti-mutated kras t cell receptors

Publications (2)

Publication Number Publication Date
NZ732045A NZ732045A (en) 2024-04-26
NZ732045B2 true NZ732045B2 (en) 2024-07-30

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