Immunotherapeutic Nano-Ghosts: A cell-free Nanometric system for Off-The-Shelf Cancer Immunotherapy

Autologous cytotoxic T lymphocytes (CTLs) has the ability to change the course of a pathology. Unfortunately, in the face of widely variable and adaptive tumors, often presenting a highly immunosuppressive environment and MHC-restriction, the possible use of CTLs is largely limited to a small number of patients and very few types of cancers. The main goal of this study was to combine the safety and tumor-targeting capabilities of mesenchymal stem cells (MSCs) with the tumor-restrictive capacity of CTLs in an inanimate platform that can withstand limiting host influences. The foundations for this combination are laid by a novel class of nano-vesicles (200 nm), termed immunotherapeutic-nano-ghosts (iNGs), equipped with membrane proteins from MSCs and exogenous ones inspired by CTLs. We used different methods to reach our goal, by fusion of NGs from different source cells and by manipulating the MSCs to express death ligands inspired by CTLs. Our iNGs system exhibited lethal effect in vitro on cancer cells and in vivo in human melanoma model where it inhibited tumor growth to the same levels as the free drug, but with 6-orders of magnitude lower effector concentration.

Abstract