Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis
The subject matter disclosed herein is generally directed to modulating anti-tumor T cell immunity by modulating steroidogenesis. Steroidogenesis may be modulated with inhibitors of enzymes that synthesize glucocorticoids in a tumor. The inhibitor may target Cyp11a1. The inhibitor may be metyrapone. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.
1. A method of altering T cell dysfunction in a subject suffering from cancer comprising administering to the subject metyrapone, wherein the metyrapone is conjugated to a bispecific antibody or antibody drug conjugate targeting the metyrapone to monocytes and/or macrophages, wherein anti-tumor immunity is enhanced in the subject, wherein the metyrapone is administered directly to the tumor microenvironment of the cancer.
2. The method of claim 1 , wherein the metyrapone is administered by intra-tumoral injection.