EP3853251A1 — Methods and pharmaceutical composition for the treatment of cancers resistant to immune checkpoint therapy

USPTO Abstract

Recent advances in the understanding of macrophage biology has revealed that tumor- associated macrophages are very heterogeneous and that several distinct subsets coexist in the tumor microenvironment. These subsets differ not only in terms of expression profile and origin but also in their pro- or anti-tumoral function. Here, the inventors describe a macrophage subset in mouse models of metastatic melanoma that express CD 163. Specific depletion of the CD 163 expressing cells in an anti-PD-l checkpoint inhibitor resistant melanoma model using cytotoxic lipid nanoparticles conjugated to αCDl63 mAh results in a massive infiltration of CD4+ and activated CD8+ T-cells. Moreover the inventors show that tumors quickly relapsed with combined treatment with anti-PDl antibodies. Thus the present invention relates to a method of treating a cancer in a subject in need thereof comprising administering to the subject a therapeutically effective combination comprising at least one immune checkpoint inhibitor and an agent capable of depleting the population of CD 163+ tumor associated macrophages.