Horizons For Immunotherapy

I'm given to note that progress in targeted therapies - in particular those that use nanoparticles like dendrimers to string together homing mechanisms with cell destruction payloads - is very important. All sorts of cells need killing as we get older, to prevent the damage they cause: cancer cells, senescent cells, and so forth. Targeted nanoparticle therapies will soon provide a broad and extensible technology platform to get that job done, for any cell whose biochemistry we know how to distinguish, thus lightening the load of age-related damage in our bodies.

When you stop to think about it, we already have a flexible, targeted cell destruction therapy roaming our bodies from day one: it's called the immune system. Immune cells are very much more sophisticated than the dendrimers being built in laboratories today, and are capable of destroying much more than just errant cells. Any biochemical that can be broken down within a cell is fair game, not just those biochemicals that make up our cells.

Looking ahead, we can see three paths:

  • The path of nanoparticles, nanoscale targeting devices and payloads to destroy the specific cells

  • The path of manipulating our immune system into destroying targeted cells and cleaning up specific biochemicals

  • The merged path: artificial cells built to have a limited subset of natural immune cell functions, and set to a specific cleanup task within the body

I expect it'll be a good 20 years or so before we see the first practical applications of artificial cells in this area, though present progress suggests less complex projects will emerge more rapidly than that. For the purposes of this post, I'm more interested in what will result from work on immune therapies over the next decade, alongside the clinical application of targeted nanoparticle therapies.

If you've been following along, you'll know that the more-than-well-funded cancer and Alzheimer's research establishments are driving early development of immune therapies. In essence, researchers are seeking ways to manipulate the immune system into destroying cancer cells more aggressively, or that it would normally leave alone, and cleaning up the buildup of amyloid compounds in the brain.

Once a technology platform is established for directing the immune system to attack and break down specific compounds in the body, I can see it having just as broad a future set of applications as cell destruction. All sorts of damaging biochemicals build up around our cells as we age, and cause great harm over the years by interfering in important metabolic processes. On the one hand we have advanced glycation end-products (AGEs) that link important molecules together and glueing up the works, on the other hand a whole range of compounds known as amyloids, but that are different from the well-known form of amyloid associated with Alzheimer's disease. The damage done by the buildup of these amyloids is in fact the most common cause of death for those supercententarians who have avoided all other common causes of death.

For example, imagine an immune therapy that directs your immune cells to attack and break down glucosepane, currently thought to be the dominant form of AGE in aged tissue, glueing up important molecules and generally making things work less well. That would be a way down the road, however.

More immediate prospects involve attacking amyloid compounds other than that involved in Alzheimer's disease. Many forms of compound build up between cells with advancing age and are collectively termed "amyloid" - and it looks feasible to rework immune therapies intended for Alzheimer's, presently in development or trial, to attack these amyloids. Such an initiative is presently in the queue at the Methuselah Foundation, awaiting funding:

The Methuselah Foundation is presently in discussion with leading researchers in this field with a view to initiating work on a vaccine - similar to that developed by Elan for Alzheimer’s disease - to stimulate the aged body to clear the widespread amyloids (particular of transthyretin) responsible for senile systemic amyloidosis.

It is good to see that many medical technologies of broad potential application are well advanced in their development cycle at this time. We'll need them to further progress in the repair of aging.

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