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Transforming the Immune System to Attack Cancer Through CAR T-cell Therapy
CAR T-cell therapy is an innovative means of boosting the immune system for cancer patients. Dr. John McCarty, Director of the Cellular Immunotherapies and Transplant Program at VCU Massey Cancer Center, discusses CAR T-cell therapy.
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Learn more about John McCarty, MD
John McCarty, MD
John McCarty, MD is the Director of the Cellular Immunotherapies and Transplant Program at VCU Massey Cancer Center.Learn more about John McCarty, MD
Transcription:
Transforming the Immune System to Attack Cancer Through CAR T-cell Therapy
Prakash Chandran (Host): Welcome to Healthy with VCU Health, where experts from VCU Health share their knowledge, cutting-edge research and the latest innovations to help you achieve optimal health and wellness. In this episode, Dr. John McCarty, Director of Cellular Immunotherapies and Transplant at VCU Massey Cancer Center discusses a rapidly emerging type of cancer therapy that reprograms patients own immune cells to treat their cancer. It’s called CAR T-cell therapy, and these treatments have captured the attention of researchers and the public because of the remarkable responses they have produced in some patients, both children and adults, for whom all other treatments had stopped working. Dr. McCarty led the first team in Virginia to offer the FDA-approved CAR T-cell therapy, and today he explains how the therapy works, who might benefit from it and the research underway to improve it and expand its use. I’m Prakash Chandran. And Dr. McCarty, let’s get right into it. What exactly is CAR T-cell therapy?
John McCarty, MD (Guest): Well it’s a way of upgrading or updating your immune system. So, for example, if you are going travelling somewhere, very often you’ll upgrade your phone or download apps that will help make it more functional like with maps or with how to do local travel and so on. And so what we’re really doing here is we’re using a method of upgrading the app of your immune system so it’s better able to attack cancers that standard therapies are just not touching.
Our immune system is supposed to recognize infections, yes, but it’s also supposed to recognize cancers. And sometimes it can’t see it, sometimes there are cells there, but they aren’t in enough numbers, and sometimes the cancers actually have a way of putting these cells to sleep. What CAR-T does is overcome those methods by which cancers can evade the immune system and become established and become a problem for patients.
Host: How exactly do you go about upgrading the system to recognize those things?
Dr. McCarty: So, we take T cells, which are some of the cells of the immune system. Now they normally have another job. Sometimes that’s to fight off the flu. Sometimes that’s to remember that measles, mumps or rubella shot that you had, sometimes it supposed to look out for colon cancer or bacteria. What we do is we take those and then isolate them. They are then updated with a new target. Basically, a virus containing the target we wish. That serves as the upgrade download. These cells they now have a second job, which is to go after a protein on the surface of a lymphoma or acute lymphoblastic leukemia or whatever we are wishing to attack, and they are then expanded, and they are activated and then brought back and re-infused into the patient.
Host: That is incredible. I feel like we are living in the future, the fact that we are able to do that. And you mentioned a couple of different types of cancers but I’m curious as to the comprehensive list that this has been developed for.
Dr. McCarty: There are two FDA-approved commercial products. One is called Yescarta, which is used to treat diffuse large cell lymphoma that is relapsed or resistant to multiple lines of therapy. The other is Kymriah and that is an agent that also is very effective in diffuse large cell lymphoma and related lymphomas but also in acute lymphoblastic leukemia for those aged 25 and younger. So, it’s used in adolescent, young adult and pediatric patients.
Host: So, you talked about the later one being applicable for people that are 25 and under but talk to me about how you identify who the right candidate is and when they should start this treatment.
Dr. McCarty: In order to make sure that patients get the right form of therapy that is going to best benefit them from not in the short term but in the long term, we decided to enhance our existing bone marrow and stem cell transplant program where traditional ways of doing cellular therapy through a transplant and bring in the CAR-T cellular therapy program. In this way, there may be patients, for example, that are on our pre-transplant list that may not respond and suddenly are eligible for CAR-T. CAR-T may be the more effective therapy. So, in general, CAR-T at this time is most effective in patients whose disease is not responding or there is a substantial amount of their lymphoma or their leukemia left behind. And we know from past experience and studies that these patients don’t do as well if we applied standard therapies.
Now there are clinical trials that are also serving to expand both the timing as well as the different types of cancers that we hope to be treating fairly certain as well. So, we are not just stopping here. We are looking to see if we can bring this to more patients and more clinical situations.
Host: Yeah, this really does seem like cutting-edge therapy, and while you alluded to this earlier, I’d love to learn a little bit more about all of the benefits that a patient undergoing CAR-T can enjoy.
Dr. McCarty: Well from the first studies with these FDA-approved products, typically these were patients who we really had no options left. And to be able to, for example in the case of non-Hodgkin’s lymphoma, to be able to offer therapy that would bring someone 60% chance or better of getting a response where they hadn’t received a response in three or even up to nine different kinds of therapies beforehand is truly remarkable.
Likewise, for pediatric and young adult patients who have ALL where the survival at two years is essentially zero, to be able to get 90% of them into remission and show that two years later that 75% of them or greater are still in that remission and staying there. I mean this is truly, truly remarkable and it really moves the needle in terms of what we will be able to offer.
Host: Yeah, it certainly is. But I’m sure that people listening to this are probably thinking this almost sounds too good to be true and one of the questions that I’m sure we are all asking is what are the potential side effects with CAR-T?
Dr. McCarty: Well, essentially these cells when they see their target, they are going to expand. They are going to become very, very, very excited and they are going to cause a very brisk and very rapid immune response. And in many patients, that is actually a very good thing because we know that the cells are expanding and that eventually they are going to become a new part of the permanent immune system and keep surveillance and keep watch for [cancer] coming back. But sometimes, that response can become very aggressive and can cause side effects.
Patients may see what we call a cytokine storm or cytokine release syndrome where they may have low blood pressure almost as though they have sepsis or blood poisoning. Or they may have an attack on their lungs and have difficulty breathing and require oxygen support or even a trip to the medical respiratory intensive care unit. Sometimes, that can even lead to changes in their thinking or their neurologic status or their ability to remember names or even sometimes as severe as seizures.
But fortunately, we have nationally and internationally, we have established a standardized set of guidelines to monitor patients but then also to have very effective interventions where we can turn off the gas that is feeding this exuberant response so that patients maintain the benefit without incurring the risk.
Host: Okay, that is helpful and it’s so good that you do monitor to make sure or I guess to minimize the amount of risk that the patient has to go through when they are going through this therapy. I’m curious about the length of time that it takes. So, let’s say someone is a good candidate for CAR-T. Tell us a little bit about how it works, how long it takes typically and walk us through that process.
Dr. McCarty: So, if someone is deemed eligible, we will do testing to make sure that they are fit and that there aren’t other medical problems that might actually incur greater risk than benefit for the rigors of this treatment. We can’t always predict who is going to have these more outsized reactions and so we treat everyone the same to make sure they are fit, and we can support them adequately.
We then do the collection of the cells. That’s basically a two- or three-hour session as an outpatient in the blood bank. And then it goes back to the central laboratories of the respective places where these are created, and it take about three weeks on average, sometimes a little less, sometimes a little longer to actually have the cells created, expanded and then shipped back to us. At that point, when we know we have the cells in hand, patients are admitted and they receive five days of chemotherapy that essentially makes room in their immune system for these new cells to be able to operate, to be able to expand and to be able to be effective.
And depending on whether someone has a more outsized reaction or not, they are in the hospital typically for about anywhere from ten days to two to three weeks thereafter.
Host: And Dr. McCarty, in closing here, is there anything else that you would like our audience to know or understand about the CAR T-cell therapy?
Dr. McCarty: Absolutely. Well we have a website through the Massey Cancer Center that talks about CAR-T, but in keeping with the Massey mission, we are not willing to be content with just what is currently FDA available. It’s not available everywhere. It’s available at specific centers that have done an extensive amount of work and program development and preparation so that we can keep patients getting the treatment appropriately but also safely.
But more than that, we see the great benefit from this. We need to learn long-term how durable this response is. We know that people who are in response six months will likely stay in remission for two years or longer. And it’s not that things are going to fall apart after that, we just don’t have the long-term data and we as a national community are learning this as we follow patients longer.
But we also want to see it for other diseases. There are other lymphomas. Perhaps for example, we have a trial here using CAR-Ts for patients who have chronic lymphocytic leukemia or it’s lymph node lymphoma-related brother. We are also even comparing it with what we standardly use for bone marrow transplant. If someone has a first relapse of their diffuse large cell lymphoma, we are comparing CAR-T against transplant to see which is more effective, which is more beneficial in terms of patients’ quality of life. And also asking the very important healthcare resource questions about how we can best manage medical healthcare resources and finances.
Finally, we are also straying into even some solid tumors where we hope soon to offer transplant for certain kinds of sarcoma and probably into certain kinds of solid tumors that may have specific protein targets on their surface. So, this is really just the beginning.
Host: Well, Dr. McCarty, this has been a fascinating conversation learning about CAR-T, so I really appreciate your time. Thank you all for listening to Healthy with VCU Health. To learn more about CAR T-cell therapy at VCU Massey Cancer Center, visit www.masseycit.org, that’s M-A-S-S-E-Y-C-I-T.org. Or call 804-828-4360. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for topics of interest to you. Thanks and we’ll see you next time.
Transforming the Immune System to Attack Cancer Through CAR T-cell Therapy
Prakash Chandran (Host): Welcome to Healthy with VCU Health, where experts from VCU Health share their knowledge, cutting-edge research and the latest innovations to help you achieve optimal health and wellness. In this episode, Dr. John McCarty, Director of Cellular Immunotherapies and Transplant at VCU Massey Cancer Center discusses a rapidly emerging type of cancer therapy that reprograms patients own immune cells to treat their cancer. It’s called CAR T-cell therapy, and these treatments have captured the attention of researchers and the public because of the remarkable responses they have produced in some patients, both children and adults, for whom all other treatments had stopped working. Dr. McCarty led the first team in Virginia to offer the FDA-approved CAR T-cell therapy, and today he explains how the therapy works, who might benefit from it and the research underway to improve it and expand its use. I’m Prakash Chandran. And Dr. McCarty, let’s get right into it. What exactly is CAR T-cell therapy?
John McCarty, MD (Guest): Well it’s a way of upgrading or updating your immune system. So, for example, if you are going travelling somewhere, very often you’ll upgrade your phone or download apps that will help make it more functional like with maps or with how to do local travel and so on. And so what we’re really doing here is we’re using a method of upgrading the app of your immune system so it’s better able to attack cancers that standard therapies are just not touching.
Our immune system is supposed to recognize infections, yes, but it’s also supposed to recognize cancers. And sometimes it can’t see it, sometimes there are cells there, but they aren’t in enough numbers, and sometimes the cancers actually have a way of putting these cells to sleep. What CAR-T does is overcome those methods by which cancers can evade the immune system and become established and become a problem for patients.
Host: How exactly do you go about upgrading the system to recognize those things?
Dr. McCarty: So, we take T cells, which are some of the cells of the immune system. Now they normally have another job. Sometimes that’s to fight off the flu. Sometimes that’s to remember that measles, mumps or rubella shot that you had, sometimes it supposed to look out for colon cancer or bacteria. What we do is we take those and then isolate them. They are then updated with a new target. Basically, a virus containing the target we wish. That serves as the upgrade download. These cells they now have a second job, which is to go after a protein on the surface of a lymphoma or acute lymphoblastic leukemia or whatever we are wishing to attack, and they are then expanded, and they are activated and then brought back and re-infused into the patient.
Host: That is incredible. I feel like we are living in the future, the fact that we are able to do that. And you mentioned a couple of different types of cancers but I’m curious as to the comprehensive list that this has been developed for.
Dr. McCarty: There are two FDA-approved commercial products. One is called Yescarta, which is used to treat diffuse large cell lymphoma that is relapsed or resistant to multiple lines of therapy. The other is Kymriah and that is an agent that also is very effective in diffuse large cell lymphoma and related lymphomas but also in acute lymphoblastic leukemia for those aged 25 and younger. So, it’s used in adolescent, young adult and pediatric patients.
Host: So, you talked about the later one being applicable for people that are 25 and under but talk to me about how you identify who the right candidate is and when they should start this treatment.
Dr. McCarty: In order to make sure that patients get the right form of therapy that is going to best benefit them from not in the short term but in the long term, we decided to enhance our existing bone marrow and stem cell transplant program where traditional ways of doing cellular therapy through a transplant and bring in the CAR-T cellular therapy program. In this way, there may be patients, for example, that are on our pre-transplant list that may not respond and suddenly are eligible for CAR-T. CAR-T may be the more effective therapy. So, in general, CAR-T at this time is most effective in patients whose disease is not responding or there is a substantial amount of their lymphoma or their leukemia left behind. And we know from past experience and studies that these patients don’t do as well if we applied standard therapies.
Now there are clinical trials that are also serving to expand both the timing as well as the different types of cancers that we hope to be treating fairly certain as well. So, we are not just stopping here. We are looking to see if we can bring this to more patients and more clinical situations.
Host: Yeah, this really does seem like cutting-edge therapy, and while you alluded to this earlier, I’d love to learn a little bit more about all of the benefits that a patient undergoing CAR-T can enjoy.
Dr. McCarty: Well from the first studies with these FDA-approved products, typically these were patients who we really had no options left. And to be able to, for example in the case of non-Hodgkin’s lymphoma, to be able to offer therapy that would bring someone 60% chance or better of getting a response where they hadn’t received a response in three or even up to nine different kinds of therapies beforehand is truly remarkable.
Likewise, for pediatric and young adult patients who have ALL where the survival at two years is essentially zero, to be able to get 90% of them into remission and show that two years later that 75% of them or greater are still in that remission and staying there. I mean this is truly, truly remarkable and it really moves the needle in terms of what we will be able to offer.
Host: Yeah, it certainly is. But I’m sure that people listening to this are probably thinking this almost sounds too good to be true and one of the questions that I’m sure we are all asking is what are the potential side effects with CAR-T?
Dr. McCarty: Well, essentially these cells when they see their target, they are going to expand. They are going to become very, very, very excited and they are going to cause a very brisk and very rapid immune response. And in many patients, that is actually a very good thing because we know that the cells are expanding and that eventually they are going to become a new part of the permanent immune system and keep surveillance and keep watch for [cancer] coming back. But sometimes, that response can become very aggressive and can cause side effects.
Patients may see what we call a cytokine storm or cytokine release syndrome where they may have low blood pressure almost as though they have sepsis or blood poisoning. Or they may have an attack on their lungs and have difficulty breathing and require oxygen support or even a trip to the medical respiratory intensive care unit. Sometimes, that can even lead to changes in their thinking or their neurologic status or their ability to remember names or even sometimes as severe as seizures.
But fortunately, we have nationally and internationally, we have established a standardized set of guidelines to monitor patients but then also to have very effective interventions where we can turn off the gas that is feeding this exuberant response so that patients maintain the benefit without incurring the risk.
Host: Okay, that is helpful and it’s so good that you do monitor to make sure or I guess to minimize the amount of risk that the patient has to go through when they are going through this therapy. I’m curious about the length of time that it takes. So, let’s say someone is a good candidate for CAR-T. Tell us a little bit about how it works, how long it takes typically and walk us through that process.
Dr. McCarty: So, if someone is deemed eligible, we will do testing to make sure that they are fit and that there aren’t other medical problems that might actually incur greater risk than benefit for the rigors of this treatment. We can’t always predict who is going to have these more outsized reactions and so we treat everyone the same to make sure they are fit, and we can support them adequately.
We then do the collection of the cells. That’s basically a two- or three-hour session as an outpatient in the blood bank. And then it goes back to the central laboratories of the respective places where these are created, and it take about three weeks on average, sometimes a little less, sometimes a little longer to actually have the cells created, expanded and then shipped back to us. At that point, when we know we have the cells in hand, patients are admitted and they receive five days of chemotherapy that essentially makes room in their immune system for these new cells to be able to operate, to be able to expand and to be able to be effective.
And depending on whether someone has a more outsized reaction or not, they are in the hospital typically for about anywhere from ten days to two to three weeks thereafter.
Host: And Dr. McCarty, in closing here, is there anything else that you would like our audience to know or understand about the CAR T-cell therapy?
Dr. McCarty: Absolutely. Well we have a website through the Massey Cancer Center that talks about CAR-T, but in keeping with the Massey mission, we are not willing to be content with just what is currently FDA available. It’s not available everywhere. It’s available at specific centers that have done an extensive amount of work and program development and preparation so that we can keep patients getting the treatment appropriately but also safely.
But more than that, we see the great benefit from this. We need to learn long-term how durable this response is. We know that people who are in response six months will likely stay in remission for two years or longer. And it’s not that things are going to fall apart after that, we just don’t have the long-term data and we as a national community are learning this as we follow patients longer.
But we also want to see it for other diseases. There are other lymphomas. Perhaps for example, we have a trial here using CAR-Ts for patients who have chronic lymphocytic leukemia or it’s lymph node lymphoma-related brother. We are also even comparing it with what we standardly use for bone marrow transplant. If someone has a first relapse of their diffuse large cell lymphoma, we are comparing CAR-T against transplant to see which is more effective, which is more beneficial in terms of patients’ quality of life. And also asking the very important healthcare resource questions about how we can best manage medical healthcare resources and finances.
Finally, we are also straying into even some solid tumors where we hope soon to offer transplant for certain kinds of sarcoma and probably into certain kinds of solid tumors that may have specific protein targets on their surface. So, this is really just the beginning.
Host: Well, Dr. McCarty, this has been a fascinating conversation learning about CAR-T, so I really appreciate your time. Thank you all for listening to Healthy with VCU Health. To learn more about CAR T-cell therapy at VCU Massey Cancer Center, visit www.masseycit.org, that’s M-A-S-S-E-Y-C-I-T.org. Or call 804-828-4360. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for topics of interest to you. Thanks and we’ll see you next time.