Published on December 30, 2020
New Strategies for CAR T-Cell Therapy in Diffuse Large B-Cell Lymphoma
A number of different strategies in CAR T-cell therapy for diffuse large B-cell lymphoma were presented at this year's American Society of Hematology (ASH) conference. Joining us to shed light on the innovative treatment methods is Dr. Stephen Ansell, MD, PhD, of the Mayo Clinic. Dr. Ansell explains how CAR T-cell therapy works and how it can be personalized to increase successful outcomes. He also shares information on bispecific antibody therapy, which is more affordable than CAR T-cell therapy, and why it may be a good option for some patients. Watch to learn more!
Transcript | CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma
Dr. Ansell: Hi, my name's Steve Ansell. I'm a Professor of Medicine at Mayo Clinic, and I chair the Lymphoma Group at the Mayo Clinic.
For patients that have diffuse large B-cell lymphoma, there's been a lot of really exciting information that came out of the most recent American Society of Hematology, the ASH meeting in 2020. And the main population of people where these results are looking really good are in patients that have relapsed disease, particularly those that have relapsed after a stem cell transplant. Many people will know that large cell lymphoma can sometimes be cured with initial therapy.
In patients where the disease comes back, there's a second chance at getting rid of the disease by doing an autologous stem cell transplant. And then in patients, if the disease comes back yet again, the question is what to do there. And in those patients, there have been two pieces of information, one of which we kind of knew, but more information became available and another which is becoming more obvious now, both of them cellular therapies and ways to make the immune system work better.
What is CAR T-Cell Therapy, and How Does it Work?
So, the first is a chimeric antigen receptor, T-cell type of treatment, CAR T-cell treatment. And what that means is, T-cells from the patient are engineered and a novel new receptor docking site, if you like, is put into those T-cells. And then those cells are put back into the patient and they stick to the cancer cell and activate, and then go after that cancer cell and get rid of it. And more and more and more information is now coming out about the results with this type of approach. And the results are looking very promising, showing that a sizable number of people can go into a good remission with this treatment and stay in remission. And we're optimistic that those are now another subset of people where we get a very durable remission and potentially even a cure.
But there've been patients where even this was not sufficient therapy and patients have subsequently progressed. So again, at the ASH meeting, a number of different strategies to really try and make these CAR T-cells better. And there've been a number of ways in which that's being tested. The first is to put in more than one docking site. So rather than it only sticks to one protein on the cancer cell, now it may stick to more than one, typically two. And the reason that's important, cancer cells get smart and take the proteins that the CAR T-cells are attacking off their surface, and that way they hide from the immune system. So putting on more than one allows you to really go after the cancer cell in a more effective fashion.
The second way in which sometimes CAR T-cells are switched off as it is, is that there are proteins that are put on the outside of the cancer cell that actually switches off the immune system. So now these CAR T-cells are being what we call armored or protected by actual blocking antibodies that will protect against these negative signals that would switch off the CAR T-cells. So the one area that's really been exciting is all of this progress in CAR T-cells, but CAR T-cells are very expensive and do have some real challenges sometimes in being able to make these cells.
What is Bispecific Antibody Therapy?
So, the other group of drugs that's really proving to be very exciting is what is called a bispecific antibody. Bispecific just means it sticks to two different things, and again, using a very similar principle to CAR T-cells. What this antibody does is it sticks to the cancer cell on the one side, and it sticks to the T-cells, the immune system on the other, and it brings them into very close proximity, right up next to each other. And when it does that, the T-cells become activated and will actually go after the cancer cell in a very similar fashion to what I mentioned with CAR T-cells.
This allows you to actually use this antibody straight off the shelf, and there are now actually at least four of these types of antibodies where really good results were reported for diffuse large B-cell lymphoma at this ASH meeting. All of them showing that a treatment can be given in a reasonably safe fashion, even though the immune system becomes activated, that activated immune system can be targeted to the malignant cell, and response rates that are significant in a majority of patients are seen. And I think the most exciting part about this is that those responses have been quite durable.
So, when you take all of that together, I think the exciting thing in diffuse large B-cell lymphoma is that immunotherapies, be it CAR T-cell treatments or immune checkpoint therapy is really proving to be very promising. And that's something that I think is potentially going to change how patients do in the long-term. Hopefully, more patients are cured of their disease.
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