Thursday, April 4, 2024

CAR-T 2.0?

A small pharma company announced today that it was submitting an Investigational New Drug (IND) application to the FDA for what they are calling "CAR-T 2.0," a newer, better version of CAR-T (or so they hope).

The treatment is called SynKIR-310, and the phase 1 trial will be patients with relapsed/refractory B-cell Lymphomas, including Diffuse Large B Cell lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, and Marginal Zone Lymphoma.

Their treatment includes a couple of differences when compared to current CAR-T treatments. They call theirs KIR-CAR, the "KIR" being "Killer-Cell Immunoglobin-like Receptors."  These help to regulate a type of immune cell called a Natural Killer (NK) cell. NK cells are a type of lymphocyte, like B cells (which turn cancerous in FL) and T cells (which is what CAR-T uses). NK cells work differently than B and T cells, which need exposure to a threat before they can eliminate them. Basically, B and T cells have to learn that a threat (like a virus or a bacteria) is a threat. NK cells can recognize cells that are damaged by disease (like cancer) and eliminate them, and then send signals to other cells that there is a problem. 

KIR-CAR is also different in that it targets a different type of protein than CAR-T usually does. CAR-T usually attaches itself to the CD19 protein, while KIR-CAR will attach itself to something very similar. 

The upshot of this, if all goes according to plan, is that SynKIR-310 will allow T cells to not have to work as hard as they do with CAR-T, meaning it will be effective longer than current CAR-T is (for some patients, CAR-T is very durable, but for about half, it stops working after a year or so, if it worked at all).

I say "if all goes according to plan" because, of course, this is very new. It has been effective on animal models, but this IND application will mean it will be tried on humans for the first time in a trial. If you follow clinical trials over the long term, you now that a pretty small percentage will ultimately end up in the doctor's office. 

Still, this is worth mentioning because it is a really good example of the kind of innovative research that is happening to make CAR-T even more effective than it is. It would be wonderful if this trial was successful and it moved on to bigger tests. 

Early, but definitely one to keep an eye on. 



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