CAR T-Cell Therapy: Could This Be a Viable Option for MPN Patients?

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Topics include: Treatment

Looking ahead at the myeloproliferative neoplasm (MPN) treatment landscape, is there promise in CAR T-cell therapy? MPN experts Dr. Angela Fleischman from UC Irvine and Dr. John Crispino from Robert H. Lurie Comprehensive Cancer Center lend insight into the future of CAR-T Cell therapy and its role in treating hematologic malignancies. Dr. Crispino also discusses the potential of another type of immunotherapy, checkpoint inhibitors, for MPN treatment. Watch now to learn what the latest research indicates about the capability of these treatments for MPN patients.

This is an MPN Research Foundation program produced by Patient Power. We thank Incyte Corporation for their support.

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Transcript

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:

Okay, we mentioned just a few minutes ago CAR T-cell therapy, and I was watching former Vice President Biden just on TV yesterday talking to John McCain’s daughter, and he was mentioning about research. He was talking about CAR-T therapy in lymphoid, as you mentioned, Dr. Fleischman, areas. So let’s just talk about this for a second, because people hear about this on the news and say, “Well, doesn’t this apply to MPN?” So first of all, Dr. Fleischman, was is CAR-T?

What does it stand for? And how does it work, and what’s the challenge in finding I guess a target for it?

Dr. Fleischman:          

So with CAR-T cells, it’s chimeric antigen receptor. Basically you take the T cells from the person with the disease, so it’s their T cells, and you engineer the T cells so as to—so T cells are killer cells. If you have infected cells, they’re killing bad cells. It’s not that T cells are very important if you develop a cancer to go and survey it. They like, I guess, guards – they see something that shouldn’t be there, they go and they kill those cells. So basically engineering that person’s T cells to recognize a protein that is specifically on the cell’s surface of the cells that they would like to target.

So if here’s the target cell, the T cell will have the receptor to go and bind to the abnormal cell, and then the T cell will kill that cell; so basically bringing the T cells to your target cells, so you need a specific target that is ideally expressed on your cancer cells, but not expressed on your normal cells. That’s why, with the calreticulin, that seems like a very easy approach because with the calreticulin mutation, it creates a new protein sequence that shouldn’t be on normal cells.

Andrew Schorr:         

Okay, so do you see the day when this CAR-T therapy, which has been used for the sickest of some lymphoid malignancy patients, young children with ALL and something people now with diffuse large B-cell lymphomas, thatwe’ll see that show up in MPNs? What do you think? 

Dr. Fleischman:          

I mean, it makes a lot of sense that it probably will, just given the excitement about CAR-T cells and how it’s being applied to so many different malignancies. It’s definitely also worth a try in myeloproliferative neoplasms. 

Andrew Schorr:         

Okay. And, Dr. Crispino, you mentioned about immunotherapy, so another approach is what we see on TV for lung cancer. They’re advertising these checkpoint inhibitors for different subtypes of lung cancer. The drugs that are advertised, pembrolizumab (Keytruda) and nivolumab (Opdivo), people see those commercials. Does that have any utility yet, or will it ever, do you think, in MPNs?

Dr. Crispino:              

So I think that there has been a trial of one of these agents with Serge Verstovsek, but I don’t think any of that was presented at this meeting. I certainly hope that some of these drugs may work, but there’s obviously a possibility that they wouldn’t have activity in the MPNs.

Andrew Schorr:         

But the whole idea, like with CAR Ts, is your immune system failed you when you started developing aberrant cells, any kind of cancer cell. So the idea is, can you boost your own immune system to do its job. Isn’t that it? 

Dr. Crispino:              

Right. So you want to reactive these cells, which are otherwise shut down, let’s say, by cancer cells.

Andrew Schorr:         

And some people obviously with myelofibrosis or with the way of transforming, as you said, to AML, have a transplant with somebody else’s immune system to try to take over, right? That is immunotherapy?

Dr. Crispino:              

Oh, bone marrow transplants? I don’t usually think about it as an immunotherapy approach, but you certainly could have a graft-versus-leukemia effect where sometimes the graft will target leukemia cells.

Andrew Schorr:         

Right, but it’s somebody else’s immune system, where yours was down, to kind of pick up the load, right? 

Dr. Crispino:              

Right, right.

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 April 4, 2018