Oncolytic Virotherapy is a form of immunotherapy that is now being tested on malignant brain tumors in children. Dr. Gregory Friedman is the principal investigator for the first-ever pediatric trial of Herpes Simplex Virus (HSV G207) in children with recurrent or progressive brain cancers.
The herpes virus, which typically causes cold sores, has been engineered to be safe for normal cells, but can infect and kill cancer cells and stimulate the patient's own immune system to attack the tumor; this provides a "one-two punch" at killing tumor cells. This Phase 1 clinical trial, funded by the National Institutes of Health and the U.S. Food and Drug Administration, is testing the safety and reliability of the virotherapy.
To maximize the benefit of this therapy, Dr. Friedman's lab focuses on determining mechanisms of therapeutic resistance by exploring the role of tumor genotype, phenotype, and microenvironment as well as cellular defense mechanisms so that newer viruses, novel combinations, and unique routes of virus delivery may be developed to circumvent resistance mechanisms.
Here to discuss Oncolytic Virotherapy is Dr. Gregory Friedman. He is an Associate Professor of Pediatrics at UAB and Children's Hospital of Alabama, and an Associate Scientist at the UAB Comprehensive Cancer Center.
For more information click here: Clinical Trial: HSV G207.
Selected Podcast
Oncolytic Virotherapy Ushers in New Era of Cancer Treatment
Featured Speaker:
He completed his pediatric residency and fellowship in pediatric hematology/oncology at UAB. He. His primary interests are pediatric neuro-oncology and conducting pediatric virotherapy and immunotherapy brain tumor research. His overarching goal is to improve outcomes for children with malignant brain tumors by developing and improving novel, targeted therapies in the lab and then translating these therapies to clinical trials.
Gregory Friedman, MD
Dr. Gregory Friedman is an Associate Professor of Pediatrics at UAB and Children's Hospital of Alabama, and an Associate Scientist at the UAB Comprehensive Cancer Center. He is a graduate of the College of William and Mary and the Medical College of Georgia.He completed his pediatric residency and fellowship in pediatric hematology/oncology at UAB. He. His primary interests are pediatric neuro-oncology and conducting pediatric virotherapy and immunotherapy brain tumor research. His overarching goal is to improve outcomes for children with malignant brain tumors by developing and improving novel, targeted therapies in the lab and then translating these therapies to clinical trials.
Transcription:
Oncolytic Virotherapy Ushers in New Era of Cancer Treatment
Tiffany Kaczorowski (Host): Welcome to Inside Pediatrics, a podcast brought to you by Children’s Hospital of Alabama in Birmingham. I’m Tiffany Kaczorowski and our guest today is Dr. Gregory Friedman. He is a pediatric Neuro-oncologist at Children’s, an associate professor of pediatrics at UAB, the University of Alabama at Birmingham and an associate scientist at UAB’s Comprehensive Cancer Center. Welcome Dr. Friedman.
Dr. Gregory Friedman (Guest): Thank you for having me today.
Tiffany: So, today we are talking about a clinical trial or study that you’re leading using a treatment called oncolytic virotherapy and it’s basically able to reduce the size of a malignant brain tumor in children. Right?
Dr. Friedman: That’s correct. What we’re using and this is an emerging therapy, where a virus is being used to target and kill a cancer cell and so that is where the virotherapy comes from and oncolytic just means that it kills cancer cells and what’s unique about this therapy is not only is it a viral therapy, but it is also an immunotherapy because when the virus infects and kills the cancer cell, what it’s doing is it replicates when it get’s inside the cell and then it can spread to nearby cells and kill those cells; at the same time, the virus stimulates the patient’s immune system to come to the area because the immune system recognizes the virus as abnormal and not supposed to be there. As the immune system comes in to remove the virus, it then can recognize the cancer cells and the cancer debris that’s there as abnormal and so the immune system then can start to target the cancer as well. So, we consider that a one two punch of the virus killing the cancer cell but also the immune system and, so we consider this an immunoviral therapy.
Tiffany: You’re using a specific virus, is that correct?
Dr. Friedman: Correct. The virus that we’re using is a herpes simplex virus which is a virus that typically causes cold sores, but the virus has been engineered to make it safe for normal cells.
Tiffany: So, explain to me a little bit about that and why this is a safe procedure.
Dr. Friedman: What they were able to determine is that you can remove a specific gene that’s responsible for the virus’s ability to harm a normal cell and when you remove that gene, that didn’t affect the ability of the virus to still get into the cancer cells and kill the cancer cells.
Tiffany: You enroll a patient for this clinical trial, for this study and then what’s involved when they get here?
Dr. Friedman: The first thing is they come, and they are screened where they have various labs drawn as well as an MRI to look at the tumor and to confirm that there is a safe route for getting a biopsy of the tumor and then they also would meet the rest of our team at that point, Dr. Johnston, our neurosurgeon who is part of this study meets the family and discusses what the surgical procedure would entail. And once we determine that the child is indeed eligible; then typically the following day, they would go to the operating room and have a biopsy taken of the tumor to confirm that it’s – there is actual tumor there and, so we have our pathologist, Dr. Rongle who looks at it immediately while they are still in the operating room to make sure that there is tumor there and then at that point, once that is confirmed, then Dr. Johnston will place a catheter, small thin catheters into the tumor anywhere between one to four catheters and then these catheters are externalized out of the skin and the scalp and the child recovers after the surgery in the ICU like they would after any typical neurosurgical procedure. The next day, then we make sure that the catheters in in the correct location with a scan and once that’s confirmed, then our pharmacy team mixes the virus at the appropriate concentration and we infuse the virus over six hours in the ICU. Once that’s complete, then our neurosurgery team comes and removes the catheters at the bedside and the patient is transferred to a floor bed and over the next couple of days we just monitor them in the hospital and then we see them at seven days after and fourteen days after, a month after and then every couple of months after that. And so, it’s a little more involved up front, with the surgical procedure, but after that, then these children don’t need any additional chemotherapy or radiation, or other types of therapy and you know we hope that we get a nice affect from the virus and that they won’t need any additional therapies for as long as possible.
Tiffany: Right. You’re also measuring the patient’s quality of life, essentially after this procedure and while that virus is working to attack the cancer cells, right?
Dr. Friedman: Correct. So, the primary purpose of the study like this which is called a phase one study is looking at safety and tolerability to make sure that this approach is safe in children. We are looking also at efficacy which is also important to make sure that we are seeing the responses in patients and then we improve survival so that we would get responses and that they wouldn’t need other types of therapies also we just improve their overall quality of life and so Dr. Avi Manswain who is a neuropsychologist in our group, meets with the families and the patients.
Tiffany: We talked a little bit about the history. You said that UAB had been studying HSV for over 30 years but really this is the only place in the world where a pediatric study such as yours and an adult study of HSV is going on at the same time. Is that right?
Dr. Friedman: That’s correct. So, on the adult side, we have a what we call a second-generation virus or a newer virus that we think, based on studies in the lab, may be even better than the virus that we are currently studying in children and so that virus is going through clinical trial in adults while we are advancing this virus clinical trials in children and so UAB and Children’s of Alabama are the only places in the world that are conducting this type of study.
Tiffany: What are you seeing, you know just kind of describe what you’re seeing that is exciting for the future of your cancer research?
Dr. Friedman: The first thing we’re seeing so far, and we are still fairly early in the study, we have treated 5 children so far, excited to see that this type of approach is possible and then of course, we have also seen some evidence that the virus appears to be replicating and killing cancer cells and we can see that based on MRI and then we’re also looking at, as I mentioned, quality of life and we are seeing some improvements in functioning as well. We are excited about the early results.
Tiffany: Very good. And you have called these kids that you are working with and will work with as more enroll in the study; you call them pioneers. Explain to me that.
Dr. Friedman: This type of therapy and this type of approach of using these catheters directly into the tumor, has never been done before in children and so, they’re pioneers in that they are paving the way for future children. I mean these children have recurrent or progressive tumors, that many have received multiple therapies with short life expectancies and so this is just the first step of this type of therapy where we anticipate hopefully advancing this forward, maybe we can move it to frontline therapies and combine this with other types of more conventional therapies but maybe can use lower doses of those types of therapies.
Tiffany: So, not only is it giving them hope in the short term, but in the long term it’s giving hope to future kids who don’t even know that they will develop a brain tumor.
Dr. Friedman: Correct and that’s a lot of pediatric oncology is like that where the research that’s been done over the past 30 years and the children that have participated on clinical trials; the breakthroughs from those have helped the next generation of children that develop cancer. So, unfortunately, not every new therapy or therapy that is tested helps every child; but what we learn from that therapy; that makes a big impact in the future. Our goal is to take what we learn, and go back to the lab and improve the therapy, make it even better, then go back to the patient and come up with new ways of giving the therapy, come up with novel combinations with the therapy so that we can help more children.
Tiffany: If a physician out there or pediatric oncologist out there is looking to maybe enroll a patient or thinks that your clinical trial might be something that their patient could benefit from; how do they get in touch?
Dr. Friedman: There’s information about the study on clinicaltrails.gov and they just have to do a search G207 which is the name of the virus that we are using, and they can find a bunch of information about the study as well as contact information there. They also can call us at our office which is 205-638-9285.
Tiffany: Well thank you so much Dr. Friedman and good luck with your study and with the clinical trials.
Dr. Friedman: Thank you so much. I appreciate it.
Tiffany: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at www.childrensal.org/insidepediatrics .
Oncolytic Virotherapy Ushers in New Era of Cancer Treatment
Tiffany Kaczorowski (Host): Welcome to Inside Pediatrics, a podcast brought to you by Children’s Hospital of Alabama in Birmingham. I’m Tiffany Kaczorowski and our guest today is Dr. Gregory Friedman. He is a pediatric Neuro-oncologist at Children’s, an associate professor of pediatrics at UAB, the University of Alabama at Birmingham and an associate scientist at UAB’s Comprehensive Cancer Center. Welcome Dr. Friedman.
Dr. Gregory Friedman (Guest): Thank you for having me today.
Tiffany: So, today we are talking about a clinical trial or study that you’re leading using a treatment called oncolytic virotherapy and it’s basically able to reduce the size of a malignant brain tumor in children. Right?
Dr. Friedman: That’s correct. What we’re using and this is an emerging therapy, where a virus is being used to target and kill a cancer cell and so that is where the virotherapy comes from and oncolytic just means that it kills cancer cells and what’s unique about this therapy is not only is it a viral therapy, but it is also an immunotherapy because when the virus infects and kills the cancer cell, what it’s doing is it replicates when it get’s inside the cell and then it can spread to nearby cells and kill those cells; at the same time, the virus stimulates the patient’s immune system to come to the area because the immune system recognizes the virus as abnormal and not supposed to be there. As the immune system comes in to remove the virus, it then can recognize the cancer cells and the cancer debris that’s there as abnormal and so the immune system then can start to target the cancer as well. So, we consider that a one two punch of the virus killing the cancer cell but also the immune system and, so we consider this an immunoviral therapy.
Tiffany: You’re using a specific virus, is that correct?
Dr. Friedman: Correct. The virus that we’re using is a herpes simplex virus which is a virus that typically causes cold sores, but the virus has been engineered to make it safe for normal cells.
Tiffany: So, explain to me a little bit about that and why this is a safe procedure.
Dr. Friedman: What they were able to determine is that you can remove a specific gene that’s responsible for the virus’s ability to harm a normal cell and when you remove that gene, that didn’t affect the ability of the virus to still get into the cancer cells and kill the cancer cells.
Tiffany: You enroll a patient for this clinical trial, for this study and then what’s involved when they get here?
Dr. Friedman: The first thing is they come, and they are screened where they have various labs drawn as well as an MRI to look at the tumor and to confirm that there is a safe route for getting a biopsy of the tumor and then they also would meet the rest of our team at that point, Dr. Johnston, our neurosurgeon who is part of this study meets the family and discusses what the surgical procedure would entail. And once we determine that the child is indeed eligible; then typically the following day, they would go to the operating room and have a biopsy taken of the tumor to confirm that it’s – there is actual tumor there and, so we have our pathologist, Dr. Rongle who looks at it immediately while they are still in the operating room to make sure that there is tumor there and then at that point, once that is confirmed, then Dr. Johnston will place a catheter, small thin catheters into the tumor anywhere between one to four catheters and then these catheters are externalized out of the skin and the scalp and the child recovers after the surgery in the ICU like they would after any typical neurosurgical procedure. The next day, then we make sure that the catheters in in the correct location with a scan and once that’s confirmed, then our pharmacy team mixes the virus at the appropriate concentration and we infuse the virus over six hours in the ICU. Once that’s complete, then our neurosurgery team comes and removes the catheters at the bedside and the patient is transferred to a floor bed and over the next couple of days we just monitor them in the hospital and then we see them at seven days after and fourteen days after, a month after and then every couple of months after that. And so, it’s a little more involved up front, with the surgical procedure, but after that, then these children don’t need any additional chemotherapy or radiation, or other types of therapy and you know we hope that we get a nice affect from the virus and that they won’t need any additional therapies for as long as possible.
Tiffany: Right. You’re also measuring the patient’s quality of life, essentially after this procedure and while that virus is working to attack the cancer cells, right?
Dr. Friedman: Correct. So, the primary purpose of the study like this which is called a phase one study is looking at safety and tolerability to make sure that this approach is safe in children. We are looking also at efficacy which is also important to make sure that we are seeing the responses in patients and then we improve survival so that we would get responses and that they wouldn’t need other types of therapies also we just improve their overall quality of life and so Dr. Avi Manswain who is a neuropsychologist in our group, meets with the families and the patients.
Tiffany: We talked a little bit about the history. You said that UAB had been studying HSV for over 30 years but really this is the only place in the world where a pediatric study such as yours and an adult study of HSV is going on at the same time. Is that right?
Dr. Friedman: That’s correct. So, on the adult side, we have a what we call a second-generation virus or a newer virus that we think, based on studies in the lab, may be even better than the virus that we are currently studying in children and so that virus is going through clinical trial in adults while we are advancing this virus clinical trials in children and so UAB and Children’s of Alabama are the only places in the world that are conducting this type of study.
Tiffany: What are you seeing, you know just kind of describe what you’re seeing that is exciting for the future of your cancer research?
Dr. Friedman: The first thing we’re seeing so far, and we are still fairly early in the study, we have treated 5 children so far, excited to see that this type of approach is possible and then of course, we have also seen some evidence that the virus appears to be replicating and killing cancer cells and we can see that based on MRI and then we’re also looking at, as I mentioned, quality of life and we are seeing some improvements in functioning as well. We are excited about the early results.
Tiffany: Very good. And you have called these kids that you are working with and will work with as more enroll in the study; you call them pioneers. Explain to me that.
Dr. Friedman: This type of therapy and this type of approach of using these catheters directly into the tumor, has never been done before in children and so, they’re pioneers in that they are paving the way for future children. I mean these children have recurrent or progressive tumors, that many have received multiple therapies with short life expectancies and so this is just the first step of this type of therapy where we anticipate hopefully advancing this forward, maybe we can move it to frontline therapies and combine this with other types of more conventional therapies but maybe can use lower doses of those types of therapies.
Tiffany: So, not only is it giving them hope in the short term, but in the long term it’s giving hope to future kids who don’t even know that they will develop a brain tumor.
Dr. Friedman: Correct and that’s a lot of pediatric oncology is like that where the research that’s been done over the past 30 years and the children that have participated on clinical trials; the breakthroughs from those have helped the next generation of children that develop cancer. So, unfortunately, not every new therapy or therapy that is tested helps every child; but what we learn from that therapy; that makes a big impact in the future. Our goal is to take what we learn, and go back to the lab and improve the therapy, make it even better, then go back to the patient and come up with new ways of giving the therapy, come up with novel combinations with the therapy so that we can help more children.
Tiffany: If a physician out there or pediatric oncologist out there is looking to maybe enroll a patient or thinks that your clinical trial might be something that their patient could benefit from; how do they get in touch?
Dr. Friedman: There’s information about the study on clinicaltrails.gov and they just have to do a search G207 which is the name of the virus that we are using, and they can find a bunch of information about the study as well as contact information there. They also can call us at our office which is 205-638-9285.
Tiffany: Well thank you so much Dr. Friedman and good luck with your study and with the clinical trials.
Dr. Friedman: Thank you so much. I appreciate it.
Tiffany: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at www.childrensal.org/insidepediatrics .