I have a new column this week on OnlySky. It’s about how genetic engineering is giving us the power to “factory reset” the immune system.
The human immune system is a marvelously complex product of evolution, adapted to target and destroy harmful viruses and bacteria, even kinds it’s never encountered before, while leaving the body’s own cells alone. But its mechanisms of tolerance aren’t perfect, and when they fail, the result is autoimmune disease: immune cells that attack the body’s organs and tissues as if they were pathogenic invaders.
A technology that was originally designed for cancer treatment is giving us the power to fix this problem. With CRISPR and other means of genetic engineering, we can recode the immune system almost like a computer programmer fixing a software bug. If the promise of this therapy is borne out in clinical trials, we’ll be able to delete the rogue cells selectively and cure autoimmune disease without the indiscriminate carpet-bombing of immunosuppressant drugs.
Read the excerpt below, then click through to see the full piece. This column is members-only, so consider signing up! Members of OnlySky also get special benefits, like a subscriber newsletter:
CAR-T therapy originated as a cancer treatment. Scientists extract killer T cells from a person’s body and rewrite the genes for their antigen receptors, giving them new receptors that are custom-designed to match the target we want them to attack. The modified T cells are induced to multiply and reinfused into the body, where they’ll hopefully go after the threat they didn’t “notice” before.
CAR-T is well-suited to treat blood cancers, like leukemia and lymphoma, that frequently arise from mutations in B cells. Scientists can modify T cells to target CD19, a protein expressed on the surface of B cells. This is considered an ideal target because you don’t need B cells to survive. If the therapy wipes out healthy B cells along with the cancerous ones, that’s fine, because the healthy ones will repopulate over time.
However, this leads to a natural followup question: Couldn’t this method also be used to treat autoimmune disease caused by rogue B cells?
We’ve known for a while that a factory reset of the immune system is possible, because ‘immune amnesia’ is one of the documented side effects of a measles infection.
That’s part of why measles vaccination is so critical (on top of the fact the measles is one of the most actively contagious diseases in the world), because catching measles can often mean catching other diseases that you were previously immune to, and it’s often the secondary infections that actually kill or disable people.
That’s a good point. I wonder if any autoimmune disease sufferers have ever tried to get measles on purpose (presuming they weren’t already vaccinated against it) as a method of treatment. Kind of like the way we used to intentionally infect people with malaria in an attempt to treat syphilis.
Very metaphorical, I take it, rather than analogical. Ah well, titles, eh?
I took a look: https://www.ncbi.nlm.nih.gov/gene/930
“Factory resetting the immune system” would mean losing all immune ‘memory’ and rebuilding it from scratch, which would require re‑exposure to every pathogen the body has ever learned.
Best as I can tell, CAR‑T doesn’t do that. It deletes the B‑cell subsystem but leaves the rest of the immune ‘settings’ intact. What CD19‑CAR‑T does is delete CD19‑positive B‑lineage cells.
So, not a factory reset.
Yes, it’s a metaphor. I still think it helps convey the idea of what CAR-T does.
When I started writing about this, I assumed the treatment would wipe out all preestablished immunities. In the course of researching the article, I found out about the existence of CD19-negative plasma cells that also secrete antibodies, which is why it doesn’t. But that’s a good thing, insofar as it means you can get this treatment without being set all the way back to immunological square one.