This week we talk about CAR Ts, lupus, and antigen-presenting cells. We also discuss Hashimoto’s, potential cures, and allergies. Recommended Book: The Avoidable War by Kevin Rudd Transcript Chimeric antigen receptors, usually shorthanded as CARs, are a type of protein structure that receives and transmits signals within biological systems. The term "CAR T cell" refers to chimeric antigen receptors that have been altered so that these structures can give T cells, which are a component of the human body's immune system, attacking stuff that our immune systems identify as being foreign or otherwise potentially harmful, it gives these T cells the ability to target specific antigens, rather than responding in a general sense to anything that seems broadly off. So while T cells are generally deployed en masse to tackle all sorts of issues all throughout our bodies all the time, CAR T cells can tell them, hey, see this specific thing? This one thing I'm pointing at? Go kill that thing. And then they do. The potential to use CAR Ts for T cell-aiming purposes started to pop up in scientific literature in the late-1980s and early-1990s, and in the mid-90s there was a clinical trial testing the theory that T cells could be guided in this way to targeted cells throughout the body that are infected with HIV. That clinical trial failed, as did tests using CAR T approaches to sic T cells on solid tumors; there just didn't seem to be enough persistence in the T cells, in their targeting, to do much good in this regard. Second-generation CARs improved upon that original model, and that led to tests with more follow-through, better focus for those guided T cells, basically, and that improved their capacity to clear solid tumors in tests. By the early 2010s, researchers were able to completely clear solid cancers from patients, leading to complete remissions in some of them, though those patients were also treated with more conventional therapies beforehand. These new approaches led to the first two FDA-approved CAR T cell treatments in the US in 2017, for a type of leukemia and a type of lymphoma. As of late-2023, there were six such treatments approved for use by the FDA, most of them leveraged only for cancer patients who didn't respond well to conventional treatments, or who continued to relapse after several rounds of cancer therapy. It's a last line of defense, at this point, in part because it's still relatively new, and in part because the current collection of CAR T therapies seem to work best when the cancers have already been weakened by other sorts of attack. What I'd like to talk about today is another potential use for this same general technology and therapy approach that, until recently, was considered to be a really pie-in-the-sky sort of dream, but which is rapidly becoming more thinkable. — There's a theory that essentially all human beings have some kind of immunodeficiency: something that our immune systems don't do well, don't do at all, or don't do in the expected, baseline way. Any one of those immunodeficiency types can result in issues throughout a person's life, ranging from a higher-than-normal susceptibility to specific infections to a tendency to accidentally target healthy cells or biota, which can then result in all sorts of secondary issues for the host of those cells or biota. One especially pernicious and increasingly common issue in this space is what's called autoimmunity, which refers to the tendency of one's immune system to attack one's own cells and tissues and organs. If these autoimmune attacks are substantial and consistent enough, they can cause a disease in the afflicted body components, and diseases caused in this way are called autoimmune diseases. You've almost certainly heard of some of the more common of these diseases: Lupus, for instance, varies in its specifics, but arises when someone's immune system attacks their skin or muscles or joint tissues or components of their nervous system