Nanobody-based depletion of protumoral tumor-associated macrophages as novel cancer therapy.

Clinical and experimental studies delineate protumorigenic roles for immune cell subsets, in particular tumor-associated macrophages or TAM. Hence, it seems plausible to target these cells and eliminate or reprogram their function, but at present the role of distinct TAM subsets in the tumor microenvironment is insufficiently understood and tools to specifically target the most protumorigenic TAM subsets in vivo are largely non-existing.
Very recent evidence, from our lab and others, identified the Macrophage Mannose Receptor (MMR, CD206) as a marker for strongly protumorigenic TAM. Indeed, MMRhi TAM were reported to contribute to diminished therapy responsiveness and tumor relapse following anti-angiogenic or vascular-disrupting therapies and chemotherapy in preclinical tumor models. Our previous work provided the first evidence that Nanobodies (Nbs), generated against mouse MMR, efficiently penetrate solid mouse tumors and specifically recognize MMRhi TAM, providing a solid basis for Nb-mediated TAM targeting.