Liposomal-Based Nanoarchitectonicsas Bispecific TCell Engagers in Neuroblastoma Therapy

Neuroblastoma (NB) is an aggressive pediatric solid tumor that lacks efficient treatment. In the past few years, the use of engineered lymphocytes endowed with chimeric antigen receptors (CAR T), which improve their natural <i>search and destroy</i> skills against tumoral cells, has provided a highly valuable strategy to eradicate tumors in a specific and safe manner. Unfortunately, despite the excellent results achieved by these cell-based therapies in liquid tumors, their efficacy in the treatment of solid malignancies is usually modest due to the existence of several biological barriers which compromise their efficacy. Herein, a strategy to guide CAR T toward NB cells based on the use of nanometric bispecific T engagers (NBTEs) is presented. These novel bispecific nanoplatforms are based on liposomes and protocells doubly functionalized with synthetic targeting moieties (<i>para</i>-aminobenzylguanidine and fluorescein) able to selectively bind to membrane cell receptors of NB and anti-FITC CAR T, respectively. The binding process of NBTEs to NB cells was monitored by confocal fluorescence microscopy showing the excellent capacity of these nanodevices to place fluorescence labels on the surface of the malignant cells. Then, NB cells previously incubated in the presence of NBTEs were rapidly detected and destroyed by anti-FITC CAR T, which confirmed the excellent capacity of these nanoplatforms to improve the natural capacity of CAR T to eradicate malignant cells. Finally, the high versatility of the NBTE design and its easy-to-tune nature would allow their rapid application to different types of solid tumors.