Laboratory Assessment of Immune Functioning | Doctors Avigan and Ludwig | IMS 2023

Hello, my name is Heinz Ludwig. I'm working at the William E. Lennon Cancer Research Institute in Vienna, Austria. And I have a keen interest in my alumna since quite some time. And it's my pleasure to be here with David Arjan, because we are both working with, in the Rumiitse session, on laboratory assessment of the immune system. So the question is, what is the immune system? Every body of us has an immune system. The main purpose of the immune system is to protect us against microbiota, microbiota, and to protect us against malignant cells, cancer cells. So the immune system is quite complex, but there are simple means to get it, let's say, very close overview. When you look at your lymphocytes, when your lymphocyte counts are high, usually this is associated with lung survival in normal people, but also in my alumna patients. So lower lymphocyte counts, very simple. If you have severe immunoglobulin suppression, so low immunoglobulins, due to tumor suppression and or due to treatment, you have a higher risk for infections, but you have also a higher risk for shorter progression of the survival. But nowadays we have much more sophisticated means to assess the immune system. Initially we used the Pax Luris Sensor Activator cell sorters to distinguish between different cell types, and what we have learned from these studies is that specific cell types, such as an increase in deregulatory cells or an increase in myeloid derived stem cells, is associated with shorter progression of survival or higher likelihood for resistance, but now we have more advanced technologies which allows us to investigate the genetic machinery of individual cells of the immune system, but not only of the immune system, also of the immune environment. And with this we get much more information. We can study the glonal evolution of myeloma from MGUS precursor states to active myeloma to resistant myeloma, and we can also identify patients which have a higher risk for transformation from precursor states to active myeloma, and we can also identify patients who have a poorer outcome, and we can study resistance mechanisms, and we can study the composition and the activity of the immune environment. So with this information we hope to be able to shape treatment to the needs of the individual patient in a better way as we did in the past. So research is ongoing, but it is a fantastic work we have learned in the past, and our hope is of course great that with this information we will be better able to manage patients with these difficult to manage disease. Thank you. All right. Hi, I'm David Abigan. I work at Beth Israel Dignis Medical Center in Boston and have the great privilege of teaming up with minds of this really exciting area of understanding how the immune system both impacts patients with myeloma and what happens with their disease, and my focus which is trying to train the immune system to target and fight against myeloma cells. There are a lot of exciting immune-based therapies that are now coming into the clinic. One of the most notable ones is CAR T cells, which have really had a profound effect in patients with relapsed and progressive disease where we see very high rates of response, and yet for a majority of patients the disease does come back, and so there's really a lot of effort to understand what exactly is happening to the immune system in patients getting CAR T cells and what might be the sources of resistance so that we might do a better job at preventing that and actually creating a more long-term effective therapy. And so we've been looking in our laboratory and as part of the general field at what happens to CAR T cells after they're infused and what happens to the native immune system after a CAR T infusion is given. And what we've been able to show is that patients who make a secondary immune response where their overall immunity against their myeloma and against other diseases are woken up in this setting can actually have a much more effective longer-term response. And so it really is some of the first evidence that there's really an important interaction between the therapies that we're giving in terms of cell-based treatments and the native immune system and how it interacts with them. Another major focus that we've looked at are cancer vaccines which are really an effort to try and stimulate primary immunity against myeloma cells within the patient. And this is something that has really been a focus for many years. We've seen the beginnings of nice immune responses and we're trying to understand how that can be used effectively to actually prevent relapse. And so there's been a lot of exciting data to understand what are the targets that are being seen. Are those targets the same between patients or are they different? And if they're the same between patients can we do a better job in essentially stimulating immune response that then becomes long-lasting. And so we've seen some exciting evidence in these immune-based studies to try and answer those questions. And we ask it in different ways. We ask it by saying do we see evidence that there are now immune cells or T cells that kill myeloma in a patient's circulation or in the bone marrow? And we can go down to a very sort of discriminating level something called single cell technologies where we tease out each immune cell and we start to understand what it's doing and what its relationship with the primary tumor. And so we really hope that this set of assays is going to really catapult us to a new place where we can use immune therapies even more effectively.