CAR T-Cell Therapy: An Overview

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Topics include: Treatment and Understanding

What is a CAR, and what role does CAR T-cell therapy play in targeted therapy?  Dr. Nicole Lamanna of Columbia University Medical Center and Dr. Michael Keating of MD Anderson Cancer Center define CARs and the associated therapy, describing how it works and its imperfections.  Listen, though, as Dr. Keating explains why CAR T-cell therapy remains a “powerful tool” in fighting CLL.

Provided by CLL Global Research Foundation, which received support from AbbVie Inc., Genentech Inc., Gilead Sciences, Pharmacyclics, Inc., Teva Pharmaceuticals and TG Therapeutics. In partnership with The University of Texas MD Anderson Cancer Center.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Andrew Schorr:

Now, another experimental area, and there’s been a lot of buzz about this over the last few years—CARs, we’ve talked about a lot on patient power and take a look.

And Dr. Melony, couple years ago did a great explanation of CARs. Dr. Wierda has too. Chimeric antigen receptors and the question was, were these CARs, which I’ll let Nicole describe, are they ready for prime time? I think the answer is no, not yet. But what’s a CAR? 

Dr. Lamanna:      

So essentially, so this is when we talk about targeted therapy. So essentially, we take a sample, we take your cells and we take them out of your body and then manipulate them in the lab to recognize on of the proteins on your CLL cells. And then, we infuse that back in, and so hopefully, that will hone in and target your CLL cells and kill them. It enhances the immune system to attack, enhances the cells to attack your CLL cells, and so it’s more targeted directed therapy. Because of that, because it revs up your own immune system to do this, there can be some significant side effects to this treatment, because it can release other cytokines and other things in your body that can cause fevers and blood pressure changes.

Andrew Schorr:

Like the worst flu you’ve ever had.

Dr. Lamanna:      

The bad flu symptoms and things like that, and so that’s you’re hearing a lot of buzz about this, because it’s also being used in acute leukemia. So a different disease, and certainly, there have been some side effects for this treatment. So is it being continued to be further developed, because we’re looking at ways to sort of minimize the toxicities of these therapies? Absolutely. Is there a role for sure in acute leukemia where we have far fewer therapies for patients in that disease? And so they’ve been used to render many of those patients free of disease and then go on to a transplant. 

So certainly, it’s in development with a little hiccups here and there. But hopefully, the technology obviously is very important, because again, it’s trying to manipulate your own immune system to attack your cancer cells. And so this will probably have broader implications even for other cancers, but we have some ways to go to make it safer for individuals. 

Andrew Schorr:

I wanna make a point about…

Dr. Keating:         

One thing we have to be aware of is that there are a lot of things that are very potent, and we get turned off by the toxicity. And when we first used fludarabine (Fludara) in acute leukemia, it was at a much higher dose. And patients became blind and paraplegic, and at one point everyone else except [MD] Anderson gave up on the drug, and it was only because there were such spectacular responses in CLL at the lower dose.

So when you have something as potent as the immune process of the chimeric antigen receptors, you’ve gotta maintain the faith until we figure out how to make it work better. But it really is a very powerful tool. One of the problems is that once you infuse the cells, they don’t last long enough, and there are some cells called natural killer cells that you can put another genetic sequence, an IL-15 sequence and keep on providing their own food.

And they last a lot longer, and in laboratory animals they cure the animals. So it’s early days but very powerful techniques.

Andrew Schorr:

So there’s a point, and you were actually just making it. So fludarabine you mentioned. Lot of people gave up on it. It ended up for me and some of the folks here being part of therapy when they learned how to use it, and it worked really well. Venclexta (Venetoclax): There were two patients who died in the early trials, because they didn’t know how powerful it was. And you mentioned tumor lysis syndrome where there was such a big cancer cell kill, that it was more than the body can handle, and they weren’t prepared for it. But now, they’ve learned how to use it and as you heard with Allen. Allen, you’re doing great on it, right? At the right dose. Okay. And you’re gonna hear more about it. So we won’t give up on this, and thank God these doctors are investigating this.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on September 1, 2017