Systemic Tumour Suppression via the Preferential Accumulation of Erythrocyte-Anchored Chemokine-Encapsulating Nanoparticles in Lung Metastases

Abstract

Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. Metastatic tumour cells are however exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential co-localization of intravenously administered erythrocytes with metastases in the lung, we show that chemokine-encapsulating nanoparticles non-covalently anchored on the surface of injected erythrocytes result in local and systemic tumour suppression in mouse models of lung metastasis. Such ‘erythrocyte-anchored’ systemic immunotherapy led to the infiltration of effector immune cells into the lungs, to in situ immunization without the need of exogenous antigens, to the inhibition of the progression of lung metastasis, to significantly extended animal survival, and to systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.