According to the National Cancer Institute, the foundations of cancer treatment have typically been surgery, chemotherapy, and radiation therapy. Now, however, immunotherapy has become what many in the cancer community now call the "fifth pillar" of cancer treatment.
One that is emerging onto the scene is an approach called adoptive cell transfer (ACT), collecting and using patients' own immune cells to treat their cancer. There are several types of ACT, but the one that seems to be closest to producing a treatment approved by the Food and Drug Administration is called CAR T-cell therapy.
In this fascinating segment, Dr.Shalini Shenoy discusses this exciting new therapy, when it might be available to the public, and when to refer to a specialist.
Selected Podcast
CAR-T Cell Therapy at Siteman Kids at St. Louis Children’s Hospital
Featured Speaker:
Learn more about Shalini Shenoy, MD
Shalini Shenoy, MD
Shalini Shenoy, MD cares for children with cancer and blood diseases. She is director of the St. Louis Children's Hospital Bone Marrow Transplant Program.Learn more about Shalini Shenoy, MD
Transcription:
CAR-T Cell Therapy at Siteman Kids at St. Louis Children’s Hospital
Melanie Cole (Host): According to the National Cancer Institute, the foundations of cancer treatment have typically been surgery, chemotherapy and radiation therapy. Now, however, immunotherapy has become in what many in the cancer community called the fifth pillar of cancer treatment. One that’s emerging onto the scene as an approach called adoptive cell transfer – collecting and using patient’s own immune cells to treat their cancer. There are several types of ACT, but the one that seems to be closest to producing a treatment approved by the Food and Drug Administration is called CAR-T cell therapy. My guest today is Dr. Shalini Shenoy. She’s a Washington University pediatric oncologist and the director of the Bone Marrow Transplant Program at St. Louis Children's Hospital. Welcome to the show, Dr. Shenoy. So, tell us a little bit about the evolution of immunotherapy, and how it's breaking onto the cancer scene.
Dr. Shalini Shenoy, MD (Guest): So, a long time ago – we have known over the years that immunotherapy, which is the immune system and the cells that are part of it, so just the lymphocytes – are able to battle cancer, and when someone develops cancer, that immune system is overwhelmed and can’t handle it anymore which is how the cancer grows. Otherwise, the cells are supposed to be there for surveillance to get rid of any risks that we face in terms of infection and in terms of cancer. So, for many years what we've been doing is collecting these cells, trying to give a dose of these cells when there is cancer and see if those cells can then route the disease, and a lot of times, it's been able to stem the disease in the past when we do a lymphocyte infusion, for example. It’s been able to take care of the cancer and deal with it. It’s not very efficient, though. You have to give a whole lot of cells; you have to deal with a lot of toxicities trying to do that, and sometimes it may work, and sometimes it may not. So, something needed to be done to improve the action of these cells and try to target them directly to where we wanted it to go; target only the tumor cells and not cause a lot of collateral damage, and that really is where immunotherapy has evolved, and that’s become much more efficient – CAR-T being one of those places.
Melanie: So tell us about CAR-T. How has that changed this landscape?
Dr. Shenoy: So CAR-T is when we are able to take lymphocytes from a patient, and then put in genetic material into those T cells so that they can directly recognize tumor-bearing cells and attack them, kill them, and get rid of the disease. So the chimeric antigen receptor which is what CAR stands for is the genetic material that’s actually put into these cells so that they become very specific to recognize a specific tumor, and the place that it's become most successful, which is what the FDA has recently approved, is in acute lymphoblastic leukemia where the B cells that cause the acute lymphoblastic leukemia have proteins on their surface such as CD 19 where these cells can come in, attack that CD19 protein, and in that process kill the cells. So, that’s just the beginning of CAR-T cells, we think, because such proteins exist on other tumors, and if we can make these cells smart enough, we could tackle more than just leukemia – the ALL – that we do at this point.
Melanie: Absolutely fascinating, Dr. Shenoy. So, what does it mean when they say CAR-T cells are the equivalent of giving patients a living drug and you're – I mean – you’re teaching these cells, correct?
Dr. Shenoy: It’s a living cell, first of all, so you're actually putting in living material that have been sort of sharpened, so to speak. So, it knows what to do once it goes into a patient. Also, these cells, once they go in, they keep circulating, and they stay alive. They stay alive for many years. So, they're sort of – not only have they routed the disease up front once they're given, but then they stick around, and they circulate, and they keep watching out for more tumor, and if it looks like it's coming back, they can attack them all over again. So, it's an on – as opposed to a drug, you give it; it does its job; it's gone. The CAR-T cells are just this living material that keeps going on and on which is the nice part about it.
Melanie: So, it's been approved for acute lymphoblastic leukemia in children which is one of the more common type of cancers in children. What else do you see – or what else do you envision it being most beneficial for?
Dr. Shenoy: So, there are efforts in place to attack other leukemias and lymphomas for starters. So, acute myeloid leukemia is our second commonest leukemia in children, and there are efforts to develop CAR-T cells against acute myeloid leukemia. It looks like what needs to happen in that setting is going to be a little different. They are going to need a transplant. They’re going to need cells from someone else to come rescue them after CAR-T cells have been used. So, each scenario’s going to be a little different. There is an effort to develop these for lymphomas, both B-cell lymphomas as well as T-cell lymphomas. The B-cell lymphoma therapy is already up and running and in place in adult patients because these lymphomas are more common in adults, and so the expansion of the CAR-Ts for other blood cancers are very robustly going on. There are also efforts to develop CAR-Ts against solid tumors. For that, we’d have to get B cells to one particular place where the tumor is, and those efforts are under way. They are currently experimental, but hopefully, in the next few years, that’s going to be reality as well.
Melanie: And you mentioned some side effects just briefly, but like all cancer therapies, you know, that can cause worrisome side effects – CAR-T therapy can cause them as well. So, what are some of the risks and benefits of it?
Dr. Shenoy: So, the cells, as they go identify tumors cells and kill them, is release the material from inside the tumor cells out into the circulation. So, that material can set up a chemical reaction; something that is called CRS for short. It's becoming a word or a pneumonic that everybody’s recognizing these days. What it stands for is cytokine release syndrome, and the larger the tumor burden, the more this chemical reaction; the more the release of the cytokine, and so what it can do is cause things like blood pressure changes, high-grade fever, a change in their vital signs. They’ll end up in the intensive care unit – something that needs to be watched for very carefully, and luckily, we have a drug that can block the effect of these cytokines. That would have to be used as soon as possible. It should this CRS show up.
Melanie: So how are you using this therapy at Siteman Kids and can you share any outcome data that you might have?
Dr. Shenoy: So, the goal is to use this medication because it needs a lot of preparation, right? You’ve got to take these cells from a patient. You’ve got to work with them. You’ve got to prepare them, and you’ve got to infuse them back again. We are using it in the setting of patients that don’t respond to standard therapy. So, acute lymphoblastic leukemia in children – if it's a good-risk leukemia; it's highly curable with a concoction of medications we have so far. We don’t need this living therapy if that is successful. The patients who fail that therapy – patients who have their disease come back despite the standard treatment; patients who have undergone transplant and have still recurred, those are the patients that are going to be benefitted by the therapy because they really have no place to go, and this therapy has given them a second life, so to speak, in very high numbers. So, that’s the patient population that we would be using it for. So, what we hope is that – it’s not just the patients we treat over here, but patients that are treated in nearby hospitals perhaps by other oncology doctors – if they fail that transplant therapy, have a fall back to come to, and we would discuss with the oncologist and treat them just like we would treat our own patients.
Melanie: So, where do you see this going? Give us a little blueprint for future research. How soon do you think that many of the other types of CAR-T cell therapy might be approved and kind of give us a little blueprint.
Dr. Shenoy: I want to say that each is going at a different pace, so the ones like I mentioned for lymphoma are already in trials for adult patients, and it's a matter of a short period of time before it’s going to be available to younger and younger children as well after the kinks or the side effects and everything have been worked out for safety. AML, acute myeloid leukemia, and the use of CAR-T cells against that is actually being perfected in the laboratory right now. So, in the next year or two, I would expect the first initial trials against acute myeloid leukemia to get started, and we from Siteman Kids are part of the national consortia of the children’s oncology group, the Pediatric Blood and Marrow Transplant Consortium. These are groups that are working very hard to gather to actually make this happen, so I think we will see the expansion of the therapy from acute lymphoblastic leukemia to many, many others very soon. At Siteman we are also working on developing CAR-T cells against T-cell leukemia which is also going to be a first-time trial, and we're doing it in conjunction with our adult oncology transplant faculty at Siteman, and so we are going to have that available for our patients and for patients who would like to come here because they failed other front-line therapy for T-cell leukemia as well.
Melanie: So, to wrap it up, in summary, doctor, tell other pediatricians what you'd like them to know about CAR-T cell therapy, and when they should refer to a specialist?
Dr. Shenoy: So, the treatment for acute lymphoblastic leukemia is pretty standardized at this point. If a patient fails that treatment and has relapsed, and if the relapse is really early or during treatment, there's not a lot of other chemotherapy that is going to help these patients. Those patients should definitely be referred for something like CAR-T cells which is novel, which is successful, and which can keep the leukemia under control as we know it right now for very, very long periods of time. And so, I would say that anybody that has failed their front-line treatment should be considered for CAR T-cell therapy, and we’re in the process of developing multiple protocols and how to give them. For example, we were giving them just one time, and that’s sort of the standard way of doing it, but we have other studies that we’re contemplating where we're looking to see how maybe a second infusion would do. So, there's going to be more coming along in the next year or two.
Melanie: Thank you so much, Dr. Shenoy for being with us today; it's an absolutely fascinating topic. A physician can refer a patient by calling Children's Direct Physician Access Line at 1-800-678-HELP. That's 1-800-678-4357. You're listening to Radio Rounds with St. Louis Children's Hospital. For more information on resources available at St. Louis Children's Hospital, you can go to stlouishildrens.org. That’s stlouischildrens.org. This is Melanie Cole. Thanks so much for listening.
CAR-T Cell Therapy at Siteman Kids at St. Louis Children’s Hospital
Melanie Cole (Host): According to the National Cancer Institute, the foundations of cancer treatment have typically been surgery, chemotherapy and radiation therapy. Now, however, immunotherapy has become in what many in the cancer community called the fifth pillar of cancer treatment. One that’s emerging onto the scene as an approach called adoptive cell transfer – collecting and using patient’s own immune cells to treat their cancer. There are several types of ACT, but the one that seems to be closest to producing a treatment approved by the Food and Drug Administration is called CAR-T cell therapy. My guest today is Dr. Shalini Shenoy. She’s a Washington University pediatric oncologist and the director of the Bone Marrow Transplant Program at St. Louis Children's Hospital. Welcome to the show, Dr. Shenoy. So, tell us a little bit about the evolution of immunotherapy, and how it's breaking onto the cancer scene.
Dr. Shalini Shenoy, MD (Guest): So, a long time ago – we have known over the years that immunotherapy, which is the immune system and the cells that are part of it, so just the lymphocytes – are able to battle cancer, and when someone develops cancer, that immune system is overwhelmed and can’t handle it anymore which is how the cancer grows. Otherwise, the cells are supposed to be there for surveillance to get rid of any risks that we face in terms of infection and in terms of cancer. So, for many years what we've been doing is collecting these cells, trying to give a dose of these cells when there is cancer and see if those cells can then route the disease, and a lot of times, it's been able to stem the disease in the past when we do a lymphocyte infusion, for example. It’s been able to take care of the cancer and deal with it. It’s not very efficient, though. You have to give a whole lot of cells; you have to deal with a lot of toxicities trying to do that, and sometimes it may work, and sometimes it may not. So, something needed to be done to improve the action of these cells and try to target them directly to where we wanted it to go; target only the tumor cells and not cause a lot of collateral damage, and that really is where immunotherapy has evolved, and that’s become much more efficient – CAR-T being one of those places.
Melanie: So tell us about CAR-T. How has that changed this landscape?
Dr. Shenoy: So CAR-T is when we are able to take lymphocytes from a patient, and then put in genetic material into those T cells so that they can directly recognize tumor-bearing cells and attack them, kill them, and get rid of the disease. So the chimeric antigen receptor which is what CAR stands for is the genetic material that’s actually put into these cells so that they become very specific to recognize a specific tumor, and the place that it's become most successful, which is what the FDA has recently approved, is in acute lymphoblastic leukemia where the B cells that cause the acute lymphoblastic leukemia have proteins on their surface such as CD 19 where these cells can come in, attack that CD19 protein, and in that process kill the cells. So, that’s just the beginning of CAR-T cells, we think, because such proteins exist on other tumors, and if we can make these cells smart enough, we could tackle more than just leukemia – the ALL – that we do at this point.
Melanie: Absolutely fascinating, Dr. Shenoy. So, what does it mean when they say CAR-T cells are the equivalent of giving patients a living drug and you're – I mean – you’re teaching these cells, correct?
Dr. Shenoy: It’s a living cell, first of all, so you're actually putting in living material that have been sort of sharpened, so to speak. So, it knows what to do once it goes into a patient. Also, these cells, once they go in, they keep circulating, and they stay alive. They stay alive for many years. So, they're sort of – not only have they routed the disease up front once they're given, but then they stick around, and they circulate, and they keep watching out for more tumor, and if it looks like it's coming back, they can attack them all over again. So, it's an on – as opposed to a drug, you give it; it does its job; it's gone. The CAR-T cells are just this living material that keeps going on and on which is the nice part about it.
Melanie: So, it's been approved for acute lymphoblastic leukemia in children which is one of the more common type of cancers in children. What else do you see – or what else do you envision it being most beneficial for?
Dr. Shenoy: So, there are efforts in place to attack other leukemias and lymphomas for starters. So, acute myeloid leukemia is our second commonest leukemia in children, and there are efforts to develop CAR-T cells against acute myeloid leukemia. It looks like what needs to happen in that setting is going to be a little different. They are going to need a transplant. They’re going to need cells from someone else to come rescue them after CAR-T cells have been used. So, each scenario’s going to be a little different. There is an effort to develop these for lymphomas, both B-cell lymphomas as well as T-cell lymphomas. The B-cell lymphoma therapy is already up and running and in place in adult patients because these lymphomas are more common in adults, and so the expansion of the CAR-Ts for other blood cancers are very robustly going on. There are also efforts to develop CAR-Ts against solid tumors. For that, we’d have to get B cells to one particular place where the tumor is, and those efforts are under way. They are currently experimental, but hopefully, in the next few years, that’s going to be reality as well.
Melanie: And you mentioned some side effects just briefly, but like all cancer therapies, you know, that can cause worrisome side effects – CAR-T therapy can cause them as well. So, what are some of the risks and benefits of it?
Dr. Shenoy: So, the cells, as they go identify tumors cells and kill them, is release the material from inside the tumor cells out into the circulation. So, that material can set up a chemical reaction; something that is called CRS for short. It's becoming a word or a pneumonic that everybody’s recognizing these days. What it stands for is cytokine release syndrome, and the larger the tumor burden, the more this chemical reaction; the more the release of the cytokine, and so what it can do is cause things like blood pressure changes, high-grade fever, a change in their vital signs. They’ll end up in the intensive care unit – something that needs to be watched for very carefully, and luckily, we have a drug that can block the effect of these cytokines. That would have to be used as soon as possible. It should this CRS show up.
Melanie: So how are you using this therapy at Siteman Kids and can you share any outcome data that you might have?
Dr. Shenoy: So, the goal is to use this medication because it needs a lot of preparation, right? You’ve got to take these cells from a patient. You’ve got to work with them. You’ve got to prepare them, and you’ve got to infuse them back again. We are using it in the setting of patients that don’t respond to standard therapy. So, acute lymphoblastic leukemia in children – if it's a good-risk leukemia; it's highly curable with a concoction of medications we have so far. We don’t need this living therapy if that is successful. The patients who fail that therapy – patients who have their disease come back despite the standard treatment; patients who have undergone transplant and have still recurred, those are the patients that are going to be benefitted by the therapy because they really have no place to go, and this therapy has given them a second life, so to speak, in very high numbers. So, that’s the patient population that we would be using it for. So, what we hope is that – it’s not just the patients we treat over here, but patients that are treated in nearby hospitals perhaps by other oncology doctors – if they fail that transplant therapy, have a fall back to come to, and we would discuss with the oncologist and treat them just like we would treat our own patients.
Melanie: So, where do you see this going? Give us a little blueprint for future research. How soon do you think that many of the other types of CAR-T cell therapy might be approved and kind of give us a little blueprint.
Dr. Shenoy: I want to say that each is going at a different pace, so the ones like I mentioned for lymphoma are already in trials for adult patients, and it's a matter of a short period of time before it’s going to be available to younger and younger children as well after the kinks or the side effects and everything have been worked out for safety. AML, acute myeloid leukemia, and the use of CAR-T cells against that is actually being perfected in the laboratory right now. So, in the next year or two, I would expect the first initial trials against acute myeloid leukemia to get started, and we from Siteman Kids are part of the national consortia of the children’s oncology group, the Pediatric Blood and Marrow Transplant Consortium. These are groups that are working very hard to gather to actually make this happen, so I think we will see the expansion of the therapy from acute lymphoblastic leukemia to many, many others very soon. At Siteman we are also working on developing CAR-T cells against T-cell leukemia which is also going to be a first-time trial, and we're doing it in conjunction with our adult oncology transplant faculty at Siteman, and so we are going to have that available for our patients and for patients who would like to come here because they failed other front-line therapy for T-cell leukemia as well.
Melanie: So, to wrap it up, in summary, doctor, tell other pediatricians what you'd like them to know about CAR-T cell therapy, and when they should refer to a specialist?
Dr. Shenoy: So, the treatment for acute lymphoblastic leukemia is pretty standardized at this point. If a patient fails that treatment and has relapsed, and if the relapse is really early or during treatment, there's not a lot of other chemotherapy that is going to help these patients. Those patients should definitely be referred for something like CAR-T cells which is novel, which is successful, and which can keep the leukemia under control as we know it right now for very, very long periods of time. And so, I would say that anybody that has failed their front-line treatment should be considered for CAR T-cell therapy, and we’re in the process of developing multiple protocols and how to give them. For example, we were giving them just one time, and that’s sort of the standard way of doing it, but we have other studies that we’re contemplating where we're looking to see how maybe a second infusion would do. So, there's going to be more coming along in the next year or two.
Melanie: Thank you so much, Dr. Shenoy for being with us today; it's an absolutely fascinating topic. A physician can refer a patient by calling Children's Direct Physician Access Line at 1-800-678-HELP. That's 1-800-678-4357. You're listening to Radio Rounds with St. Louis Children's Hospital. For more information on resources available at St. Louis Children's Hospital, you can go to stlouishildrens.org. That’s stlouischildrens.org. This is Melanie Cole. Thanks so much for listening.