Abstract C224: Anti-CSF-1R antibodies reduce tumor-associated macrophages and inhibit tumor growth in preclinical models.

Abstract In cancer, increased infiltration of macrophages within and surrounding the tumor mass correlates with increased tumor invasiveness and growth. In addition, presence of tumor-associated macrophages (TAMs) has been shown to correlate with poor prognosis, particularly in breast, prostate, ovarian and cervical cancer. TAM proliferation, differentiation and survival is dependent on CSF-1R activation, a type III integral membrane tyrosine kinase receptor selectively expressed on cells of the mononuclear phagocyte lineage. The ligands CSF-1 and the more recently identified IL-34 are responsible for the binding and activation of CSF-1R on macrophage surfaces. While CSF-1R levels are infrequently increased in tumors compared to analogous normal tissues, increased levels of CSF-1 and IL-34 in sera of cancer patients is more frequently observed and is associated with poor prognosis and severity of disease in multiple cancers, again primarily in breast, prostate and ovarian cancer patients. Given that TAMs enhance tumor growth and that activation of the CSF-1R pathway is required for TAM function, an antibody against mouse CSF-1R was generated for proof-of-principle studies. This study summarizes the in vitro and in vivo characterization of an anti-mouse CSF-1R antibody designated CS7. CS7 was shown to inhibit the binding of both CSF-1 and IL-34 to murine CSF-1R and inhibit CSF-1R activation. More importantly, monocytic to macrophage differentiation in vitro was impeded in the presence of CS7. CS7 was evaluated in several mouse tumor models and shown to have good in vivo efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C224.