IP Library › Granted Patent US 10,138,271
Granted Patent B2
US 10,138,271 · App. 14/370,595 · Granted Nov 27, 2018

Native and agonist CTL epitopes of the MUC1 tumor antigen

Inventors: Jeffrey Schlom (Potomac, MD); Kwong-Yok Tsang (Bethesda, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
C07K7/06A61K9/127A61K35/17A61K38/193A61K39/0011A61K45/06C07K14/4727C07K14/4748A61K38/00A61K2039/5154A61K2039/5158A61K2039/585Y02A50/466
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Quick Facts
Patent No.
US 10,138,271
App. No.
14/370,595
Granted
Nov 27, 2018
Kind
B2
Abstract

The invention provides peptides comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) mucin 1 (MUC1) and analogs thereof, which can be used in vaccine prevention or therapy of cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Claims (32)

1. A method of enhancing an immune response against a MUC1-expressing cancer in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising

(i) a poxvirus vector comprising a nucleic acid encoding a peptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32, or

(ii) a liposome comprising a peptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32,

wherein the immune response in the subject is enhanced.

2. The method of claim 1 , wherein the poxvirus vector is selected from the group consisting of orthopoxvirus, avipox, capripox, and suipox virus.

3. The method of claim 1 , wherein the peptide comprises at least two of the amino acid sequences selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

4. The method of claim 1 , wherein the peptide comprises at least three of the amino acid sequences selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

5. The method of claim 1 , wherein the peptide comprises SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

6. The method of claim 1 , wherein the poxvirus vector further comprises a nucleic acid encoding at least one immunostimulatory/regulatory molecule.

7. The method of claim 6 , wherein the at least one immunostimulatory/regulatory molecule is selected from the group consisting of interleukin (IL)-2, IL-4, IL-6, IL-12, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, B7.1, B7.2, ICAM-1, LFA-3, CD70, RANTES, G-CSF, OX-40L, 41 BBL, anti-CTLA-4, and combinations thereof.

8. A method of enhancing an immune response against a MUC1-expressing cancer in a subject comprising:

(a) administering to the subject a therapeutically effective amount of a first recombinant poxvirus vector comprising a nucleic acid encoding a peptide; and

(b) administering to the subject a therapeutically effective amount of a second recombinant poxvirus vector comprising a nucleic acid encoding a peptide;

wherein the peptides of (a) and (b) are the same and comprise at least one of the amino acid sequences selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32, and

wherein the immune response in the subject is enhanced.

9. The method of claim 8 , wherein the peptide comprises at least two amino acid sequences selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

10. The method of claim 8 , wherein the peptide comprises the amino acid sequences of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

11. The method of claim 8 , wherein the first and second recombinant poxvirus vectors each further comprise a nucleic acid encoding at least one immunostimulatory/regulatory molecule.

12. The method of claim 11 , wherein the at least one immunostimulatory/regulatory molecule is selected from the group consisting of interleukin (IL)-2, IL-4, IL-6, IL-12, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, B7.1, B7.2, ICAM-1, LFA-3, CD70, RANTES, G-CSF, OX-40L, 41 BBL, anti-CTLA-4, and combinations thereof.

13. The method of claim 8 , wherein the first and second recombinant poxvirus vectors are selected from the group consisting of orthopox, avipox, capripox, and suipox virus.

14. The method of claim 13 , wherein the first recombinant poxvirus vector is an orthopox virus and the second poxvirus recombinant vector is an avipox virus.

15. The method of claim 10 , wherein the first and second recombinant poxvirus vectors each further comprise a nucleic acid encoding at least one immunostimulatory/regulatory molecule.

16. The method of claim 15 , wherein the at least one immunostimulatory/regulatory molecule is selected from the group consisting of B7.1, B7.2, ICAM-1, LFA-3.

17. A method of enhancing an immune response against a MUC1-expressing cancer in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising a poxvirus vector comprising a nucleic acid encoding a peptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32, wherein the immune response in the subject is enhanced.

18. The method of claim 17 , wherein the poxvirus vector is selected from the group consisting of orthopoxvirus, avipox, capripox, and suipox virus.

19. The method of claim 18 , wherein the poxvirus vector is selected from the group consisting of an orthopoxvirus and an avipox.

20. The method of claim 19 , wherein the poxvirus vector is an orthopoxvirus selected from the group consisting of vaccinia virus and a modified vaccinia Ankara (MVA) virus.

21. The method of claim 20 , wherein the poxvirus vector further comprises a nucleic acid encoding at least one immunostimulatory/regulatory molecule.

22. The method of claim 21 , wherein the at least one immunostimulatory/regulatory molecule is selected from the group consisting of B7.1, B7.2, ICAM-1, LFA-3.

23. The method of claim 1 , wherein the composition comprises (ii) a liposome comprising a peptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 29, and SEQ ID NO: 32.

24. The method of claim 23 , wherein the composition comprises a liposome comprising a peptide comprising SEQ ID NO: 29.

25. The method of claim 23 , wherein the composition comprises a liposome comprising a peptide comprising SEQ ID NO: 32.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2014
From: SCHLOM, JEFFREY; TSANG, KWONG-YOK
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 033640/0640 →
Continuity (2)
Provisional Application 61582723 · Jan 3, 2012
Related Publication 20140363495A1 · Dec 11, 2014