Put a patient receive a BCMA-directed CAR T cell and then use a different CAR T cell target if they relapse. There are other things involved. It's not just the target. It's the CAR T cell on the other end. So you have different components that play a role. It's not just the target. Even if you had a perfect target, if you had T cells that don't work, the perfect target won't help. So there are so many more components. If you look at not just the target, so let's say you have different options with regard to targets, you will still use an individual's T cells if we're talking about autologous CAR T cells and not about allogeneic CAR T cells, off-the-shelf products and so forth. If you talk about autologous CAR T cells, then you have to keep in mind that this is an individual. The individual has a certain history, a certain medical history, so and so many previous treatments, different types of treatments. So I don't even want to use the word quality, but the characteristics of their T cells, of their own immune cells, will vary a lot between patients. And that's a very important point because we've shown we don't have too many biomarkers telling us whether a treatment, a CAR T cell treatment, will work in a given patient. What we know that the activity level and the proliferation, so proliferative activity of their CAR T cells play a very important role. So how exhausted are your T cells at the time we give you a certain CAR T cell treatment? So again, same questions. If the question is, can we use different approaches over time, one after the other? Yes, you can. Of course, the target most likely won't change. On the target side of things, everything will look perfect, but on the T cell side of things, things will have changed over time. So your T cells will be more exhausted than when you did the first type of CAR T cell And with the third round, it will be worse, most likely. So that's something that we need to keep in mind. On the side of your own immune system, things will not get better over time. How do you test the strength of your T cells? There are some very simple things that will tell you something about the reactivity of your CAR T cells. And that's something you want to know, how well do they grow? It's very simple. If these cells grow very well, if your CAR T cells grow very well in the lab, in the test tube basically, then you know that they are still very active and they have a lot of potential. If they grow only very slowly, then that will tell you that they're probably already exhausted from all the prior treatments. And that's very interesting because it's not just the way they grow in the lab, in the test tube and so forth. This correlates very nicely with how well they grow in the patient, these cells. And talking about persistence and long-term remissions and maybe even cure, you would like the cells to persist for a while and grow in the patient as well. So that's a very important biomarker by itself. But then people have developed other biomarkers as well. And I'm working with, I'm on the biomarker committee for the Society for the Immunotherapy of Cancer. And we just started an initiative where we look into biomarkers for CAR T cell treatments and other cellular immunotherapies as well, because we think that's an enormously important question. So we have some answers, but there are a lot of questions left at this point.
HealthTree • September 7, 2025