Compositions and methods for personalized neoplasia vaccines

Patent metadata

Field	Value
Publication number	US-2016101170-A1
Application number	US-201514877125-A
Country	US
Kind code	A1
Filing date	Oct 7, 2015
Priority date	Apr 7, 2013
Publication date	Apr 14, 2016
Grant date	—

Abstract

The invention provides a method of making a personalized neoplasia vaccine for a subject diagnosed as having a neoplasia, which includes identifying a plurality of mutations in the neoplasia, analyzing the plurality of mutations to identify a subset of at least five neo-antigenic mutations predicted to encode neo-antigenic peptides, the neo-antigenic mutations selected from the group consisting of missense mutations, neoORF mutations, and any combination thereof, and producing, based on the identified subset, a personalized neoplasia vaccine.

First claim

What is claimed is:

1 . A method of making a personalized neoplasia vaccine for a subject diagnosed as having a neoplasia, comprising:
identifying a plurality of mutations in the neoplasia; analyzing the plurality of mutations to identify a subset of at least five neo-antigenic mutations predicted to encode neo-antigenic peptides, the neo-antigenic mutations selected from the group consisting of missense mutations, neoORF mutations, and any combination thereof; and producing, based on the identified subset, a personalized neoplasia vaccine.

2 . The method of claim 1 , wherein identifying further comprises:
sequencing the genome, transcriptome, or proteome of the neoplasia.

3 . The method of claim 1 , wherein analyzing further comprises:
determining one or more characteristics associated with the subset of at least five neo-antigenic mutations predicted to encode neo-antigenic peptides, the characteristics selected from the group consisting of molecular weight, cysteine content, hydrophilicity, hydrophobicity, charge, and binding affinity; and ranking, based on the determined characteristics, each of the neo-antigenic mutations within the identified subset of at least five neo-antigenic mutations.

4 . The method of claim 3 , wherein the top 5-30 ranked neo-antigenic mutations are included in the personalized neoplasia vaccine.

5 . The method of claim 3 , wherein the neo-antigenic mutations are ranked according to the order shown in FIG. 8 .

6 . The method of claim 4 , wherein the personalized neoplasia vaccine comprises at least about 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

7 . The method of claim 4 , wherein the personalized neoplasia vaccine comprises one or more DNA molecules capable of expressing at least about 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

8 . The method of claim 4 , wherein the personalized neoplasia vaccine comprises one or more RNA molecules capable of expressing at least 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

9 . The method of claim 1 , wherein the personalized neoplasia vaccine comprises neoORF mutations predicted to encode a neoORF polypeptide having a Kd of ≦500 nM.

10 . The method of claim 1 , wherein the personalized neoplasia vaccine comprises missense mutations predicted to encode a polypeptide having a Kd of ≦150 nM, wherein the native cognate protein has a Kd of ≧1000 nM or ≦150 nM.

11 . The method of claim 6 , wherein the at least about 20 neo-antigenic peptides range from about 5 to about 50 amino acids in length.

12 . The method of claim 6 , wherein the at least about 20 neo-antigenic peptides range from about 15 to about 35 amino acids in length.

13 . The method of claim 6 , wherein the at least about 20 neo-antigenic peptides range from about 18 to about 30 amino acids in length.

14 . The method of claim 6 , wherein the at least about 20 neo-antigenic peptides range from about 6 to about 15 amino acids in length.

15 . The method of claim 6 , wherein the at least about 20 neo-antigenic peptides are 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids in length.

16 . The method of claim 1 , wherein the personalized neoplasia vaccine further comprises an adjuvant.

17 . The method of claim 1 , wherein the adjuvant is selected from the group consisting of poly-ICLC, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, GM-CSF, IC30, IC31, Imiquimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, Juvlmmune, LipoVac, MF59, monophosphoryl lipid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, OK-432, OM-174, OM-197-MP-EC, ONTAK, PepTel®, vector system, PLGA microparticles, resiquimod, SRL172, Virosomes and other Virus-like particles, YF-17D, VEGF trap, R848, beta-glucan, Pam3Cys, Aquila's QS21 stimulon, vadimezan, and AsA404 (DMXAA).

18 . The method of claim 17 , wherein the adjuvant is poly-ICLC.

19 . A method of treating a subject diagnosed as having a neoplasia with a personalized neoplasia vaccine, comprising:
identifying a plurality of mutations in the neoplasia; analyzing the plurality of mutations to identify a subset of at least five neo-antigenic mutations predicted to encode expressed neo-antigenic peptides, the neo-antigenic mutations selected from the group consisting of missense mutations, neoORF mutations, and any combination thereof; producing, based on the identified subset, a personalized neoplasia vaccine; and administering the personalized neoplasia vaccine to the subject, thereby treating the neoplasia.

20 . The method of claim 19 , wherein identifying further comprises:
sequencing the genome, transcriptome, or proteome of the neoplasia.

21 . The method of claim 19 , wherein analyzing further comprises:
determining one or more characteristics associated with the subset of at least five neo-antigenic mutations predicted to encode expressed neo-antigenic peptides, the characteristics selected from the group consisting of molecular weight, cysteine content, hydrophilicity, hydrophobicity charge, and binding affinity; and ranking, based on the determined characteristics, each of the neo-antigenic mutations within the identified subset of at least five neo-antigenic mutations.

22 . The method of claim 21 , wherein the top 5-30 ranked neo-antigenic mutations are included in the personalized neoplasia vaccine.

23 . The method of claim 21 , wherein the neo-antigenic mutations are ranked according to the order shown in FIG. 8 .

24 . The method of claim 22 , wherein the personalized neoplasia vaccine comprises at least 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

25 . The method of claim 22 , wherein the personalized neoplasia vaccine comprises one or more DNA molecules capable of expressing at least 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

26 . The method of claim 22 , wherein the personalized neoplasia vaccine comprises one or more RNA molecules capable of expressing at least 20 neo-antigenic peptides corresponding to the neo-antigenic mutations.

27 . The method of claim 19 , wherein the personalized neoplasia vaccine comprises neoORF mutations predicted to encode a neoORF polypeptide having a Kd of ≦500 nM.

28 . The method of claim 19 , wherein the personalized neoplasia vaccine comprises missense mutations predicted to encode a polypeptide having a Kd of ≦150 nM, wherein the native cognate protein has a Kd of ≧1000 nM or ≦150 nM.

29 . The method of claim 24 , wherein the at least 20 neo-antigenic peptides range from about 5 to about 50 amino acids in length.

30 . The method of claim 24 , wherein the at least 20 neo-antigenic peptides range from about 15 to about 35 amino acids in length.

31 . The method of claim 24 , wherein the at least 20 neo-antigenic peptides range from about 18 to about 30 amino acids in length.

32 . The method of claim 24 , wherein the at least 20 neo-antigenic peptides range from about 6 to about 15 amino acids in length.

33 . The method of claim 24 , wherein the at least 20 neo-antigenic peptides are 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids in length.

34 . The method of

Assignees

• Broad Inst Inc
• Dana Farber Cancer Inst Inc
• Gen Hospital Corp

Inventors

• Hacohen Nir
• Wu Catherine Ju-Ying
• Fritsch Edward F

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/80

  Vaccine for a specifically defined cancer · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title