Yeast-derived nanocarriers enable binary reprogramming macrophages for cancer immunotherapy

Abstract

Tumor-associated macrophages (TAMs) play an important role in promoting tumor growth and metastasis, thus reprogramming TAMs to modulate the tumor immune microenvironment is a promising tumor treatment stratagem. Here, we present novel yeast-derived nanocarriers (YNCs) as IPI-549 delivery system for binary reprogramming of TAMs to induce anticancer immunity. The nanocarriers were fabricated from yeast cell walls with immune-oncology agent IPI-549 loading and coated with a shielding polymer for prolonged blood circulation. After intravenous injection, these YNCs could accumulate at the tumor site and be phagocytosed by TAMs via the Dectin-1 pathway to induce macrophage polarization towards M1 phenotype. In combination with IPI-549, the YNC system has efficiently inhibited tumor growth and modulated the tumor immune microenvironment through macrophage phenotypic alteration and increase of T cell-mediated antitumor immunity, which was demonstrated in a 4T1 orthotopic breast cancer mouse model. All these features indicate the promising values of our YNC delivery system in clinical antitumor applications.