Combination therapy of antibodies against human csf-1r and uses thereof

A method for treating a patient having a CSF-1R expressing tumor or having a tumor with CSF-1R expressing macrophage infiltrate, wherein the tumor is characterized by an increase of CSF-1R ligand, the method comprising administering an antibody that specifically binds to human CSF-1R and a cancer immunotherapy, wherein the cancer immunotherapy is selected from the group consisting of:

• a) T cell engaging agents selected from the group consisting of agonistic antibodies which bind to human OX40, to GITR, to CD27, or to 4-1BB, and T-cell bispecific antibodies (e.g. T cell-engaging BiTE™ antibodies CD3-CD19, CD3-EpCam, CD3-EGFR), IL-2 (Proleukin), Interferon (IFN) alpha, antagonizing antibodies which bind to human CTLA-4 (e.g. ipilimumab), to PD-1, to PD-L1, to TIM-3, to BTLA, to VISTA, to LAG-3, or to CD25;
• b) targeting immunosuppression:
• antibodies or small molecules targeting STAT3 or NFkB signaling, blocking IL-6, IL-17, IL-23, TNFa function;
• c) cancer vaccines/enhance dendritic cell function:
• OncoVex (oncolytic virus secreting GM-CSF), an agonistic CD40 antibody, Toll-like receptor (TLR) ligands, TLR agonists, recombinant fusion protein encoding MAGE-A3, PROSTVAC;
• and
• d) adoptive cell transfer:
• GVAX (prostate cancer cell line expressing GM-CSF), dendritic cell vaccine, adoptive T cell therapy, adoptive CAR T cell therapy.

A method for determining whether a subject having a cancer is a candidate for an anti-CSF-1R antibody-based cancer treatment regimen, the method comprising:

• ex vivo or in vitro determining in vitro the level of one or more of the following markers:
• CSF-1R, CD68/CD163, CD68/MHC class II, CD31 (microvessel density), and Ki67 and other markers like e.g. immuninfiltrates;
• in a sample of the subject, wherein the sample is selected from the group consisting of tissue, blood, serum, plasma, tumor cells and circulating tumor cells;
• and
• wherein a change in the level of one or more of CSF-1R, CD68/CD163, CD68/MHC class II, CD31 (microvessel density) and Ki67 and other markers like e.g. immuninfiltrates (e.g. T cells (e.g. CD4- and/or CD8-T cells), as compared with to the corresponding level in an individual not suffering from cancer, is indicative that the subject is a candidate for the anti-CSF-1 R antibody-based cancer treatment regimen.

A method for determining whether a subject having a cancer is a candidate for a therapy comprising an anti-CSF-1R antibody, the method comprising:

• ex vivo or in vitro determining in vitro the level of one or more of the following markers:
• CSF-1, Trap5b, sCD163, IL-34;
• in a sample of the subject, wherein the sample is selected from the group consisting of tissue, blood, serum, plasma, tumor cells and circulating tumor cells;
• and
• wherein a change in the level of one or more of CSF-1, Trap5b, sCD163, IL-34, as compared with to the corresponding level in an individual not suffering from cancer, is indicative that the subject is a candidate for the therapy.

A method for determining whether a subject having a cancer is a candidate for an anti-CSF-1R antibody-based cancer treatment regimen, the method comprising:

• ex vivo or in vitro determining in vitro the level of one or more of the following markers:
• IFNγ, TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, GM-CSF, VEGF, MCP-1, CCL18, CCL22, MIP-1, Galectin 3, IL1Ra, TGF alpha;
• in a sample of the subject, wherein the sample is selected from the group consisting of tissue, blood, serum, plasma, tumor cells and circulating tumor cells;
• and
• wherein a change in the level of one or more of IFNγ, TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, GM-CSF, VEGF, MCP-1, CCL18, CCL22, MIP-1, Galectin 3, IL1Ra, TGF alpha, as compared with to the corresponding level in an individual not suffering from cancer, is indicative that the subject is a candidate for the anti-CSF-1 R antibody-based cancer treatment regimen.