Kras peptide vaccine compositions and method of use

Patent metadata

Field	Value
Publication number	US-2021213120-A1
Application number	US-201816483332-A
Country	US
Kind code	A1
Filing date	Feb 5, 2018
Priority date	Feb 3, 2017
Publication date	Jul 15, 2021
Grant date	—

Abstract

The present disclosure provides compositions and methods of eliciting an anti-tumor immune response and treating cancer comprising at least one peptide of KRAS.

First claim

1 . A vaccine composition comprising (1) (i) at least one peptide of KRAS, wherein the peptide comprising an amino acid sequence selected from the group consisting of SEQ ID Nos., 4, 5, 6, 7, 8, 9, 10, 11, 12 or an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID Nos. 4-12, or (ii) a vector comprising a nucleic acid sequence encoding the peptide sequence of any one of SEQ ID Nos. 4-12 or an amino acid sequence having at least 70% sequence identity to the amino acid of any one of SEQ ID Nos. 4-12; and (2) an adjuvant, wherein the vaccine composition elicits an anti-tumor immune response in a subject.

2 . The vaccine composition of claim 1 , wherein the vaccine composition comprising at least two WIC class II peptides of KRAS, wherein the at least two peptides of KRAS are selected from SEQ ID Nos. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and combinations thereof found in Table 1 or an amino acid sequence having at least 70% sequence identity to any one of SEQ ID NO.1-12.

3 . The vaccine composition of claim 1 , wherein the vaccine composition comprising at least three peptides of KRAS, wherein the at least four peptides of KRAS are selected from SEQ ID Nos. 1-12 and combinations thereof found in Table 1 or an amino acid sequence having at least 70% sequence identity to SEQ ID NO. 1-12.

4 . The vaccine composition of claim 1 , wherein the vaccine composition comprising at least four peptides of KRAS, wherein the at least four peptides of KRAS are selected from SEQ ID Nos. 1-12 found in Table 1 or an amino acid sequence having at least 70% sequence identity to SEQ ID NO. 1-12.

5 . The vaccine composition of claim 1 , wherein the at least one peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1-12.

6 . The vaccine composition of claim 1 , wherein the vaccine composition comprises at least four peptides, wherein the four peptides comprise the amino acid sequence of SEQ ID NO: 1 (P5-21WT: KLVVVGAGGVGKSALTI), 4 (P17: SALTIQLIQNHFVDE), 6 (P78: FLCVFAINNTKSFED) and 8 (P156: FYTLVREIRKHKEKM) or an amino acid sequence having at least 70% sequence identity to SEQ ID NO. 1, 4, 6 and 8.

7 . The vaccine composition of claim 1 , wherein the vaccine composition comprises at least four peptides, wherein the four peptides comprise the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6 or an amino acid sequence having at least 70% sequence identity to SEQ ID NO. 1, 2, 4 and 6.

8 . The vaccine composition of claim 1 , wherein the adjuvant is selected from the group consisting of GM-CSF, cyclic dinucleotide (CDN), Aluminum, monophosphoryl lipid A (MPL), and STING ligands (cGAMP).

9 . The vaccine composition of claim 1 , wherein the vaccine composition further comprises a pharmaceutically acceptable carrier.

10 . A vector comprising an isolated nucleic acid sequence comprising at least one nucleic acid sequence encoding at least one peptide selected from the group consisting of SEQ ID Nos. 1-12 or an amino acid sequence having at least 70% sequence identity to SEQ ID Nos. 1-12 operatively linked to a heterologous transcriptional regulatory element.

11 . (canceled)

12 . A method of eliciting an anti-tumor immune response in a subject in need thereof, the method comprising:
administering an effective amount a vaccine composition of claim 1 to the subject, wherein the vaccine composition elicits an anti-tumor immune response.

13 . (canceled)

14 . The method of claim 12 , wherein the anti-tumor immune response reduced the number of tumor cells in a subject or tumor size in the subject.

15 . The method of claim 12 , wherein the method further comprises:
administering to the subject at least one checkpoint inhibitor.

16 . The method of claim 15 , wherein the checkpoint inhibitor is administered co-currently with the vaccine composition.

17 . The method of claim 15 , wherein the checkpoint inhibitor is selected from the group consisting of anti-PDL1 antibody, anti-VISTA antibody, TIM3 antibody, CTLA-4 antibody, PD-1 peptide, PDL-1 peptide, small molecule PD-1 inhibitor, and a combination thereof.

18 . The method of claim 17 , wherein the checkpoint inhibitor is at least one PD-1 peptide, at least one PD-L1 peptide, at least one small molecule PD-1 inhibitor, or a combination thereof.

19 . The method of claim 12 , wherein the method further comprises administering at least one NSAIDS to the subject.

20 . The method of claim 12 , wherein the method further comprises administering a RXR agonist, wherein the RXR agonist is selected from the group consisting of bexarotene, UAB30, and low dose retinoic acid.

21 . The method of claim 12 , wherein the method further comprises administering avasimibe in combination with the Kras-vaccine in an effective amount to elicit an antitumor response.

22 . The method of claim 12 wherein the subject is a human suffering from a cancer that contains a KRAS mutation.

23 . The method of claim 12 , wherein the subject is a human with lung cancer, pancreatic cancer, or colon cancer.

24 . The method of claim 12 , wherein the method further comprises treating the subject with irradiation or chemotherapy.

25 . A method to reduce or slow the progression or development of cancer in a patient at risk of developing a KRAS-associated cancer, the method comprising:
determining if a patient is at risk of developing a KRAS associated cancer; and treating the patient with a vaccine composition of claim 1 .

26 . The method of claim 25 , wherein the step of determining if a patient is at risk of developing a KRAS associated cancer comprises:
detecting a mutation of KRAS in a sample from the patient.

27 . (canceled)

28 . (canceled)

29 . The method of claim 25 , wherein the treating step further comprises administering Avasimibe with the vaccine in an effective amount to treat the cancer.

30 . The method of claim 25 , wherein the treating step further comprises administering a checkpoint inhibitor, the checkpoint inhibitor is selected from the group consisting of anti-PDL1 antibody, anti-VISTA antibody, TIM3 antibody, CTLA-4 antibody, PD-1 peptide, PDL-1 peptide, small molecule PD-1 inhibitor, and a combination thereof, wherein the combination of the vaccine and checkpoint inhibitor in combination reduce or slow the progression or development of cancer.

31 . (canceled)

32 . The method of claim 31 , wherein the at least one PD-1 peptide, at least one PD-1 peptide or combinations thereof are selected from SEQ ID NO: 33-54 and combinations thereof.

33 . The method of claim 25 , wherein the method further comprises administering at least one RXR agonist, wherein the RXR agonist is selected from the group consisting of bexarotene, UAB30, and low dose retinoic acid.

34 . (canceled)

Assignees

• Medical College Wisconsin Inc

Inventors

• Pan Jing
• You Ming
• Lubet Ronald

Classifications

• A61K39/001164 Primary

  GTPases, e.g. Ras or Rho · CPC title

• A61K39/0011

  Cancer antigens · CPC title

• A61K2039/82

  Colon · CPC title

• A61K2039/852

  Pancreas · CPC title

• A61K31/255

  of sulfoxy acids or sulfur analogues thereof · CPC title