Combination therapy with semaphorin-4D blockade (SEMA4D) and DC1 therapy

Patent metadata

Field	Value
Publication number	US-12201719-B2
Application number	US-202318307920-A
Country	US
Kind code	B2
Filing date	Apr 27, 2023
Priority date	Jun 21, 2019
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

Disclosed are compositions and methods comprising the administration of pulsed dendritic cells and an immunoregulator molecule inhibitor for the treatment of cancer.

First claim

What is claimed is:

1. A method of treating a human epidermal growth factor 2 (HER2) positive cancer in a subject comprising administering to the subject an anti-cancer combination therapy comprising at least one dendritic cell pulsed with a HER2 oncodriver administered intratumorally and at least one immunoregulatory molecule inhibitor comprising an antibody or an antigen-binding fragment thereof that binds specifically to Semaphorin 4D (SEMA4D), wherein said immunoregulatory molecule inhibitor is administered systemically; and wherein administration of the combination therapy results in tumor shrinkage of injected and non-injected tumors.

2. The method of claim 1 , wherein the HER2 oncodriver pulsed dendritic cell is activated with interleukin 12 (IL-12) prior to administration.

3. The method of claim 1 , wherein the antagonist antibody that specifically binds to SEMA4D comprises pepinemab.

4. The method of claim 1 , wherein prior to administering to the subject, the dendritic cells are removed from the subject and pulsed with the HER2 oncodriver ex vivo.

5. The method of claim 1 , wherein the HER2 oncodriver pulsed dendritic cells are administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 30, 31, 45 days, or 2, 3, 4, 5, or 6 months prior to administration of the at least one immunoregulatory molecule inhibitor.

6. The method of claim 1 , wherein the at least one dendritic cell pulsed with a HER2 oncodriver is administered concurrently with the at least one immunoregulatory molecule inhibitor.

7. The method of claim 1 , wherein the at least one immunoregulatory molecule inhibitor is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 30, 31, 45 days, 2, 3, 4, 5, or 6 months prior to administration of the HER2 oncodriver pulsed dendritic cells.

8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof blocks SEMA4D binding to its receptor.

9. The method of claim 1 , wherein administration of the anti-cancer combination therapy results in tumor shrinkage of injected and non-injected tumors.

10. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) comprising VH complementarity determining regions (VHCDRs) 1-3 comprising SEQ ID NOS 5, 6, and 7, respectively and a variable light chain (VL) comprising VL complementarity determining regions (VLCDRs) 1-3 comprising SEQ ID NOs 8, 9, and 10, respectively.

11. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL comprising the amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4, respectively.

12. The method of claim 1 , wherein the cancer is a HER2 positive cancer selected from breast cancer, melanoma, colorectal cancer, pancreatic cancer, prostate cancer, bladder cancer, ovarian cancer, stomach cancer, any combination thereof, or any metastasis thereof.

13. The method of claim 12 wherein the cancer is HER2-positive breast cancer.

14. The method of claim 13 , wherein the cancer is metastatic HER2-positive breast cancer.

Assignees

• H Lee Moffitt Cancer Center And Res Institute Inc A Florida Non Profit Corporation
• Vaccinex Inc

Inventors

• Czerniecki Brian
• Kodumudi Krithika N
• Evans Elizabeth

Classifications

• A61K2039/5154

  Antigen presenting cells [APCs], e.g. dendritic cells or macrophages · CPC title

• A61K39/0011

  Cancer antigens · CPC title

• A61K39/001106 Primary

  Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4 · CPC title

• A61K39/001102

  Receptors, cell surface antigens or cell surface determinants · CPC title

• A61K9/0019 Primary

  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