US-20260125459-A1 - Macrophage depletion and vesicular stomatitis virus for treatment of cancer

US20260125459A1US 20260125459 A1US20260125459 A1US 20260125459A1US-20260125459-A1

Abstract

The present invention relates to the treatment of cancers and in particular to the treatment of cancers with a macrophage depleting agent and a recombinant vesicular stomatitis virus.

Inventors

Melissa MAYR
Monika PETERSSON

Assignees

BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Dates

Publication Date: 20260507
Application Date: 20251014
Priority Date: 20241015

Claims (7)

1 . A method of treating cancer in a subject comprising administering an antagonistic antibody which is directed against CSF1 or CSFR to the subject and further comprising administering a recombinant vesicular stomatitis virus to the subject and thereby treating the cancer, wherein in said vesicular stomatitis virus the gene coding for the glycoprotein G of the vesicular stomatitis virus is replaced by the gene coding for the glycoprotein GP of lymphocyte choriomeningitis virus (LCMV), and/or the glycoprotein G is replaced by the glycoprotein GP of LCMV.
2 . The method according to claim 1 , wherein the cancer is a solid cancer.
3 . The method according to claim 1 , wherein the cancer is selected from the list consisting of: a reproductive tumor, an ovarian tumor, a testicular tumor, an endocrine tumor, a gastrointestinal tumor, a pancreatic tumor, a liver tumor, a kidney tumor, a colon tumor, a colorectal tumor, a bladder tumor, a prostate tumor, a skin tumor, melanoma, a respiratory tumor, a lung tumor, a breast tumor, a head & neck tumor, a head and neck squamous-cell carcinoma (HNSCC) and a bone tumor.
4 . The method according to any one of the preceding claims , wherein the recombinant vesicular stomatitis virus is administered concomittantly, sequentially or alternately with the antagonistic antibody.
5 . The method according to any one of claims 1-4 , wherein the antagonistic antibody is selected from the group consisting of axatilimab, emactuzumab, cabiralizumab, AMG820LY3022855, or IMC-CS4.
6 . A composition comprising an antagonistic antibody which is directed against CSF1 or CSFR and a recombinant vesicular stomatitis virus, wherein in said vesicular stomatitis virus the gene coding for the glycoprotein G of the vesicular stomatitis virus is replaced by the gene coding for the glycoprotein GP of lymphocyte choriomeningitis virus (LCMV), and/or the glycoprotein G is replaced by the glycoprotein GP of LCMV in said vesicular stomatitis virus.
7 . A kit of parts comprising: a) A recombinant vesicular stomatitis virus or a pharmaceutical composition comprising said recombinant vesicular stomatitis virus, wherein in said vesicular stomatitis virus the gene coding for the glycoprotein G of the vesicular stomatitis virus is replaced by the gene coding for the glycoprotein GP of lymphocyte choriomeningitis virus (LCMV), and/or the glycoprotein G is replaced by the glycoprotein GP of LCMV in said vesicular stomatitis virus, and b) an antagonistic antibody which is directed against CSF1 or CSFR.

Description

RELATED APPLICATIONS This application claims the benefit of European Patent Application No. EP 24206598.5, filed Oct. 15, 2024. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on Aug. 25, 2025, is named 01-3606-US-1_SL.xml and is 16,085 bytes in size. FIELD OF THE INVENTION The present invention relates to the treatment of cancers and in particular to the treatment of cancers with a macrophage depletion agent and a recombinant vesicular stomatitis virus. BACKGROUND OF THE INVENTION The rationale to target macrophages, either by repolarization or depletion, to fight cancer exists since 1985. Macrophages are well known to play a pivotal role in anti-viral defense mechanisms. In general, macrophages within the tumor are impacting immune surveillance due to impacting anti-tumor immune cell activity and creating an immune suppressive environment. Among different agents that have been subjected to clinical trials, it has been shown that CSF1R inhibition preferentially eliminates M2 immunosuppressive macrophage and resulted in a change in the ratio of CD8/CD4 T-cell levels, indicating a conversion towards a more immuno-competent TME. Wild-type vesicular stomatitis virus (VSV) is capable to infect macrophages, especially sub-capsular sinus macrophages within the spleen. It has been well established that these viruses can replicate within these macrophages for one or two cycles. In turn, macrophages can stimulate type I Interferon signalling, thereby blocking virus replication and limiting viral spread. Corroborating findings have been reported for the capability of VSV-GP (a recombinant VSV expressing the glycoprotein of LCMV instead of the wild-type glycoprotein) to transiently infect specialized CD169+ve macrophage populations within the spleen and liver. However, little is known about the role of macrophages and VSV-GP replication within in the tumor. SUMMARY OF THE INVENTION It is to be understood that any embodiment relating to a specific aspect might also be combined with another embodiment also relating to that specific aspect, even in multiple tiers and combinations comprising several embodiments to that specific aspect. The present invention provides in a first aspect, a method of treating cancer in a subject, comprising administering a macrophage depleting agent to the subject and thereby treating the cancer. In an embodiment, relating to the first aspect, the cancer is a solid cancer. In a related embodiment, the cancer is selected from the list consisting of: a reproductive tumor, an ovarian tumor, a testicular tumor, an endocrine tumor, a gastrointestinal tumor, a pancreatic tumor, a liver tumor, a kidney tumor, a colon tumor, a colorectal tumor, a bladder tumor, a prostate tumor, a skin tumor, melanoma, a respiratory tumor, a lung tumor, a breast tumor, a head & neck tumor, a head and neck squamous-cell carcinoma (HNSCC) and a bone tumor. In an embodiment, relating to the first aspect or any of its embodiments, the method further comprises administering a recombinant vesicular stomatitis virus to the subject. In a related embodiment, the gene coding for the glycoprotein G of the vesicular stomatitis virus is replaced by the gene coding for the glycoprotein GP of lymphocyte choriomeningitis virus (LCMV), and/or the glycoprotein G is replaced by the glycoprotein GP of LCMV. In a further related embodiment, the recombinant vesicular stomatitis virus is administered concomittantly, sequentially or alternately with the macrophage depleting agent. In an embodiment, relating to the first aspect or any of its embodiments, the macrophage depleting agent is a colony-stimulating factor receptor (CSFR) inhibitor. In a related embodiment, the CSFR inhibitor blocks CSFR on tumor associated macrophages. In a further related embodiment, the CSFR inhibitor is an antagonistic antibody which is directed against CSFR, preferably CSF1R. In another embodiment, the CSFR inhibitor is selected from the group consisting of ataxilimab, emactuzumab, cabiralizumab, pexidartinib, edicotinib, sotuletinib, ARRY-382, AMG820, GW2580, PLX7486, Ki20227, LY3022855 IMC-CS4, PLX3397 or PLX5622. In an embodiment, relating to the first aspect or any of its embodiments, the macrophage depleting agent is a colony-stimulating factor 1 (CSF1) inhibitor. In a related embodiment, the CSF1 inhibitor is an antagonistic antibody which is directed against CSF1. In a second aspect, the invention relates to a composition comprising a macrophage depleting agent and a recombinant vesicular stomatitis virus. In a third aspect, the invention relates to a kit of parts comprising: a) a recombinant vesicular stomatitis virus or a pharmaceutical composition comprising said recombinant vesicular stomatitis virus, andb) a macrophage depleting agent. It will be understood that any of the herein disclosed methods