Nanotics Aims at Preventing Senescent Cells from Evading Immune Surveillance

Nanotics works on a nanoparticle platform that can modulate cell signaling via depletion of arbitrary target signaling molecules, something that has a great many potential uses, such as altering the behavior of the immune system. Given the present level of interest in clearance of senescent cells as an approach to treating aging, it isn't surprising to see platform companies of this ilk turning their attention to the production of senolytic treatments in addition to their existing pipelines. Here the approach is to deny lingering senescent cells the capacity to protect themselves against immune surveillance, and thus enable the immune system to destroy a greater fraction of these errant cells than would otherwise be the case.

Many cell signals are normally delivered in an intelligent cell-mediated way, meaning that one cell actually moves through the body until it's quite close to a target cell, before releasing the appropriate signal molecules. This greatly increases the likelihood that only the target cell - and not an "off-target" cell - will receive the signal. However, in various diseases, the delivery of the signal molecule is dysregulated in some way, sometimes because a cell is secreting a signal molecule systemically rather than focally to a target cell. The cell that receives this signal molecule - which it would not have received under normal circumstances - may do something it shouldn't do, which can manifest at the tissue level as disease. But the target cell may in fact be responding in a perfectly appropriate way to an incorrect signal. Most medicine still focuses on tissues and organs, rather than the underlying cells and signal molecules.

In cancer, the main problem is not the existence of cancer cells - which the immune system routinely clears out - but rather that cancer cells sometimes persist long enough to erect an inhibitory shield. The secreted molecules inhibit either the immune system's killer cells or the "death signals" those cells produce. There are times when this type of inhibitory signaling is completely appropriate. For instance, the fetus must inhibit the mother's immune system in order to survive, given that's genetically only half the mother and thus looks like an invader. Cancer not only mimics the process used by the fetus/placenta but employs many of the same molecules to do it.

For anti-aging, one would deplete the various known pathogenic signaling molecules that increase with age. Many of these are inflammatory and are responsible for what's termed inflammaging. We are also designing an approach to deplete immune inhibitors secreted by senescent cells for their defense, as a new generation of senolytic therapy. For the vast majority of non-genetic diseases, the drivers or enablers of the disease are signal molecules or molecular signal inhibitors. All of these targets can be depleted by our approach, without drugs and thus without the side effects of drugs.