This article details the development and preclinical testing of a novel cancer immunotherapy called MiTEs (myeloid-targeted immunocytokines and natural killer (NK)/T cell enhancers). The researchers engineered MiTEs to overcome the immunosuppressive tumor microenvironment by simultaneously targeting Tumor-Associated Macrophages (TAMs) and activating effector lymphocytes (T and NK cells). Specifically, MiTEs are masked IL-2 cytokines fused to an antagonistic anti-TREM2 antibody, ensuring the toxic IL-2 component is only activated within the tumor by a TAM-specific protease, MMP14. Extensive spatial and single-cell RNA sequencing data from human and mouse tumors demonstrate that MiTEs effectively reprogram TAMs, induce robust anti-tumor immunity, and show superior efficacy and minimal toxicity compared to conventional checkpoint inhibitors in preclinical models.

References:

• von Locquenghien M, Zwicky P, Xie K, et al. Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy[J]. Cell, 2025.