iNano-Ghosts: A cell-free nanometric system for off-the-shelf cancer immunotherapy

MSCs are the focus of intensive efforts for developing cell therapies for a broad range of diseases. Oncological applications building on MSC allogeneic safety and their ability to home in on multiple tumors commonly involve ex vivo MSC manipulations to secrete cancer-toxic biologicals. Clinical studies testing this approach have been mostly disappointing, due to MSCs susceptibility to host-induced changes. Independently, T cell therapies have already produced remarkable clinical outcomes in cancer. Still, the most significant challenges in this form of immunotherapy remain its highly individualized nature and sensitivity to host immunosuppression.

We hypothesize that overcoming these challenges can be realized by combining the safety and tumor-targeting capabilities of 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 nanovesicles (200 nm), termed immuno-nano-ghosts (iNGs), equipped with the membrane proteins of MSCs and CTLs. On top of retaining MSC active tumor-targeting ability and benefiting from a nanometric size allowing them to utilize the enhanced permeability and retention effect, such iNGs should be able to attack tumors via their cytotoxic CTL components. This can be accomplished while overcoming resistance and evading the immune system by retaining MSCs’ immunomodulatory mechanisms. Our foundational results have established the safety of nano-ghosts (NG) derived from MSCs (MSC-NG) and their ability to target multiple tumor models. Also, we have demonstrated the cytotoxic activity of MSC-NGs expressing CTL-inspired membrane proteins as well as developed procedures for NG production from T cells. The anticipated technological outcome of this project will be an off-the-shelf immunomimetic therapeutic compound integrating biological elements allowing it to target and selectively eradicate tumors and applicable for multiple malignancies, including metastatic and brain tumors. Importantly, by requiring no patient cells and by overcoming the susceptibility of living cells to limiting host-induced changes, products based on the iNGs should be more widely available and applicable than MSC and T cell therapies.