Methods and compositions for treating cancer with ecm-affinity peptides linked to immunotherapeutic antibodies

Patent metadata

Field	Value
Publication number	US-2023377764-A1
Application number	US-202318164164-A
Country	US
Kind code	A1
Filing date	Feb 3, 2023
Priority date	Apr 20, 2017
Publication date	Nov 23, 2023
Grant date	—

Abstract

The methods and compositions described herein address the need in the art by providing compositions and methods for a therapy with an antibody that is specifically targeted to and/or retained intra- or peri-tumorally, limiting systemic exposure and reducing side-effects. Accordingly, aspects of the disclosure relate to a composition comprising an immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide. An ECM-affinity peptide is one that has affinity for an extracellular matrix protein.

First claim

1 . A composition comprising an immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide.

2 . The composition of claim 1 , wherein the ECM-affinity peptide comprises a peptide from placenta growth factor-2 (PlGF-2).

3 . The composition of claim 2 , wherein the peptide from PlGF-2 is at least 85% identical to SEQ ID NO:1.

4 . (canceled)

5 . The composition of claim 1 , wherein the peptide comprises a von Willebrand factor (VWF) peptide.

6 . (canceled)

7 . The composition of claim 5 , wherein the VWF peptide comprises a peptide that is at least 85% identical to SEQ ID NO:3, SEQ ID NO:11, SEO ID NO:14, or fragments thereof.

8 . (canceled)

9 . The composition of claim 1 , wherein the peptide comprises a CXCL-12 peptide.

10 . (canceled)

11 . The composition of claim 9 , wherein the CXCL-12 peptide is at least 85% identical to SEQ ID NO:2.

12 - 14 . (canceled)

15 . The composition of claim 1 , wherein the immunotherapeutic antibody comprises a CTLA4, PD-L1, or PD-1 antibody.

16 . (canceled)

17 . The composition of claim 1 , wherein the immunotherapeutic antibody comprises a CD40 agonistic antibody.

18 - 19 . (canceled)

20 . The composition of claim 1 , wherein the composition further comprises a second immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide.

21 . The composition of claim 20 , wherein the composition comprises;
a CTLA4 antibody operatively linked to an ECM-affinity peptide; and (a) a PD-L1 antibody operatively linked to an ECM-affinity peptide or (b) a PD-1 antibody operatively linked to an ECM-affinity peptide.

22 . (canceled)

23 . A method for treating cancer in a subject comprising administering the composition of claim 1 to a subject.

24 . (canceled)

25 . The method of claim 23 , wherein the administered dose of the antibody operatively linked to the peptide is less than the minimum effective dose of the antibody administered without the peptide.

26 .- 38 . (canceled)

39 . The method of claim 23 , wherein the method further comprises administration of a second immunotherapeutic antibody operatively linked to a an extracellular matrix (ECM)-affinity peptide.

40 . The method of claim 39 , wherein the method comprises;
administration of a CTLA4 antibody operatively linked to an ECM-affinity peptide; and (a) administration of a PD-L1 antibody operatively linked to an ECM-affinity peptide or (b) administration of a PD-1 antibody operatively linked to an ECM-affinity peptide.

41 - 42 . (canceled)

43 . The method of claim 23 , wherein the cancer is metastatic cancer comprising at least a first tumor and a second tumor, and wherein the composition is administered peri-tumorally or intra-tumorally to the first tumor and is not administered peri-tumorally or intra-tumorally to the second tumor.

44 - 45 . (canceled)

46 . The composition of claim 1 , wherein the immunotherapeutic antibody comprises an αGITR, αCD134, or αCD137 antibody.

47 .- 49 . (canceled)

50 . The composition of claim 1 , wherein the ECM-affinity peptide comprises a decorin peptide.

51 . The composition of claim 50 , wherein the decorin peptide comprises SEQ ID NO:16 or comprises a peptide that is at least 85% identical to SEQ ID NO:16.

52 - 53 . (canceled)

54 . A method of treating cancer in a patient comprising administering a CD40 agonistic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide, wherein the patient has a cancer that is resistant to an immune checkpoint therapy.

55 .- 57 . (canceled)

Assignees

• Univ Chicago

Inventors

• Hubbell Jeffrey A
• Ishihara Jun
• Ishihara Ako
• Fukunaga Kazuto
• Swartz Melody

Classifications

• G21F5/12 Primary

  Closures for containers; Sealing arrangements · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K38/18

  Growth factors; Growth regulators · CPC title

• A61K38/195

  Chemokines, e.g. RANTES · CPC title