Granted Patent
B2
US 12,220,450 · App. 17/397,447 · Granted Feb 11, 2025
Complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for treatment of colorectal cancer
Assignee:
Amal Therapeutics SA
A61K39/0011A61K38/10A61K38/17A61K38/177A61K38/18A61K47/42A61K47/64A61K47/6425A61K47/6803A61K47/6811A61K47/6865A61P1/00A61P35/00C07K7/06C07K7/08C07K14/47C07K14/475C07K19/00C12N5/10A61K2039/5154A61K2039/6031C07K2319/02C07K2319/03C07K2319/10C07K2319/33C07K2319/40C12N2710/16233Y02A50/30
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Abstract
The present invention provides a novel complex for use in the prevention and/or treatment of colorectal cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of colorectal cancer, such as a pharmaceutical compositions and vaccines are provided.
Claims (61)
1. A method for treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject a complex comprising:
a) a cell penetrating peptide;
b) at least one antigen or antigenic epitope; and
c) at least one toll-like receptor (TLR) peptide agonist, wherein the at least one TLR peptide agonist is a TLR2 and/or TLR4 peptide agonist; and
wherein the components a)—c) are covalently linked.
2. The method according to claim 1 , wherein the complex is a recombinant polypeptide or a recombinant protein.
3. The method according to claim 2 , wherein the components a) to c) are positioned in N-terminal→C-terminal direction in the order:
(α) component a)—component b)—component c); or
(β) component c)—component a)—component b).
4. The method according to claim 3 , wherein the components are linked by a further component.
5. The method according to claim 4 , wherein the components are linked by a linker or a spacer.
6. The method according to claim 1 , wherein the cell penetrating peptide:
(i) has an amino acid length of 5 to 50 amino acids in total; and/or
(ii) has an amino acid sequence comprising a fragment of the minimal domain of ZEBRA, said minimal domain extending from residue 170 to residue 220 of the ZEBRA amino acid sequence according to SEQ ID NO: 3, wherein, optionally, 1, 2, 3, 4, or 5 amino acids have been substituted, deleted, and/or added without abrogating said peptide's cell penetrating ability.
7. The method according to claim 6 , wherein the length of the amino acid sequence of said cell penetrating peptide is 10 to 45 amino acids in total.
8. The method according to claim 7 , wherein the length of the amino acid sequence of said cell penetrating peptide is 15 to 45 amino acids in total.
9. The method according to claim 1 , wherein the cell penetrating peptide has an amino acid sequence comprising or consisting of an amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18), or a variant thereof sharing at least 90% sequence identity to SEQ ID NOs 6, 7, 8 or 11 without abrogating said peptide's cell penetrating ability.
10. The method according to claim 1 , wherein the at least one antigen or antigenic epitope comprises at least one tumor epitope.
11. The method according to claim 10 , wherein the at least one tumor epitope is an epitope of an antigen selected from the group consisting of EpCAM, HER-2, MUC-1, TOMM34, RNF 43, KOC1, VEGFR, βhCG, survivin, CEA, TGFβR2, p53, OGT, CASP5, COA-1, MAGE, MAGE-A3, SART and IL13Ralpha2.
12. The method according to claim 11 , wherein the complex comprises
a) one or more epitopes of EpCAM or a functional variant thereof;
b) one or more epitopes of MUC-1 or a functional variant thereof;
c) one or more epitopes of survivin or a functional variant thereof;
d) one or more epitopes of CEA or a functional variant thereof; and/or
e) one or more epitopes of MAGE-A3 or a functional variant thereof.
13. The method according to claim 12 , wherein the complex comprises
a) a fragment of EpCAM comprising one or more epitopes or a functional variant thereof;
b) a fragment of MUC-1 comprising one or more epitopes or a functional variant thereof;
c) a fragment of survivin comprising one or more epitopes or a functional variant thereof;
d) a fragment of CEA comprising one or more epitopes or a functional variant thereof; and/or
e) a fragment of MAGE-A3 comprising one or more epitopes or a functional variant thereof.
14. The method according to claim 10 , wherein the at least one tumor epitope is an epitope of a neoantigen.
15. The method according to claim 14 , wherein the at least one tumor epitope is a colorectal cancer specific neoantigen.
16. The method according to claim 1 , wherein the complex comprises more than one antigen or antigenic epitope.
17. The method according to claim 1 , wherein the at least one TLR peptide agonist comprises an amino acid sequence according to SEQ ID NO: 15 or a variant thereof sharing at least 90% sequence identity to SEQ ID NO:_15 without abrogating said peptide's TLR ability.
18. The method according to claim 1 , wherein the at least one antigen or antigenic epitope comprises at least one colorectal cancer epitope.
19. The method according to claim 18 , wherein the complex comprises 3, 4, 5, 6, 7, 8, 9, 10 or more antigen or antigenic epitopes.
20. The method according to claim 1 , wherein the at least one antigen or antigenic epitope consists of one tumor epitope.
21. The method according to claim 1 , wherein the at least one TLR peptide agonist consists of the amino acid sequence according to SEQ ID NO: 15.
22. The method according to claim 1 , wherein the at least one antigen or antigenic epitope consists of one colorectal cancer epitope.
23. A method for treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject a vaccine comprising at least one of:
(i) a complex comprising
a) a cell penetrating peptide;
b) at least one antigen or antigenic epitope; and
c) at least one TLR2 peptide agonist and/or TLR4 peptide agonist; wherein the components a)—c) are covalently linked;
(ii) a nucleic acid encoding the complex as defined (i);
(iii) a vector comprising the nucleic acid as defined in (ii);
(iv) a host cell comprising the vector as defined in (iii); or
(v) a cell loaded with a complex as defined in (i).
24. A method for treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising at least one complex comprising
a) a cell penetrating peptide;
b) at least one antigen or antigenic epitope; and
c) at least one TLR2 peptide agonist and/or TLR4 peptide agonist; wherein the components a)—c) are covalently linked;
and a pharmaceutically acceptable carrier.
25. A method for treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject a combination of
(i) a complex comprising
a) a cell penetrating peptide;
b) at least one antigen or antigenic epitope; and
c) at least one TLR2 peptide agonist and/or TLR4 peptide agonist; wherein the components a)—c) are covalently linked; and
(ii) a chemotherapeutic agent, a targeted drug and/or an immunotherapeutic agent.
26. The method according to claim 25 , wherein the chemotherapeutic agent, the targeted drug and/or the immunotherapeutic agent is an immune checkpoint modulator.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 9, 2021
From: DEROUAZI, MADIHA; BELNOUE, ELODIE
To: AMAL THERAPEUTICS SA
Reel/Frame 058063/0364 →
Priority Claims (2)
WO PCT/EP2015/000580
· Mar 16, 2015
· international
WO PCT/EP2015/002244
· Nov 9, 2015
· international
Continuity (2)
Continuation
15557649
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