ICIS 2014* Targeting Inflammatory Cytokines in Cancer (#S-4)
Cancers are driven by complex networks of cytokines and chemokines that enable communication between the malignant cells and the many other cell types of the tumor microenvironment.
Pre-clinical experiments have shown that targeting these networks with therapeutic antibodies or small molecule inhibitors can decrease tumor growth and spread. The challenge now is to translate these promising results to clinical trial. This talk will focus on the cytokine IL-6 and the chemokine receptor CCR4.
IL-6 is a key regulator of an inflammatory cytokine network of high-grade serous ovarian cancer, HGSC. Clinical, pre-clinical and in silico experiments showed that antibodies to IL-6 can have multiple actions within the tumor microenvironment including reductions in cytokine production, tumor angiogenesis and tumor macrophage infiltrate as well as reducing paraneoplastic thrombocytosis. We are now investigating rational combinations of anti-IL-6 antibodies with other treatments in pre-clinical studies based with a particular emphasis on combinations with growth factor receptor inhibitors and inhibitors of angiogenesis.
The chemokine receptor CCR4 is abnormally expressed on malignant cells as well as on leukocytes in human renal cell cancer, RCC. Patient plasma levels of the CCR4 ligands and their ratio reflect this abnormality and have prognostic significance. Both a small molecule CCR4 inhibitor and an anti-CCR4 antibody had anti-tumor activity in an RCC model with a novel mechanism of action on tumor-associated macrophages that was dependent on CD4 T cell function.
Results from the pre-clinical experiments with both of these targets have the potential to be progressed to clinical trial.
