Magnetic Nanoclusters Armed with Responsive PD-1 Antibody Synergistically Improved Adoptive T-Cell Therapy for Solid Tumors.

Abstract

Although adoptive T-cell therapy has been successful in hematological malignancy treatment, its application in solid tumors remains a great challenge. Here, using a pH-sensitive benzoic-imine bond and inverse electron-demand Diels-Alder cycloaddition, we prepared magnetic nanoclusters (NCs) armed with responsive PD-1 antibody (aP), which could then bind onto effector T cells due to their PD-1 expression. After adoptive transfer, the magnetization and superparamagnetism of NCs enabled us to magnetically recruit effector T cells and aP simultaneously to tumor sites with MRI guidance. Owing to the acidic intratumoral microenvironment, the benzoic-imine bond then hydrolyzed, leading to the release of aP. The therapeutic effects of adoptive T cells and free aP could thus be spatiotemporally coupled. As a result, we achieved inhibition of tumor growth with few side effects, demonstrating the great promise of such a chemical approach for safe and high-performance adoptive T-cell therapy against solid tumors.