Bruce Levine Interview Transcript
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BRUCE MCCABE: Hello and welcome to FutureBites, where we explore pathways to a better future. I'm Bruce McCabe and my guest today is Bruce Levine who's a professor in cancer gene therapy at the University of Pennsylvania in Philadelphia. He's also the Deputy Director of Technology Innovation and Assessment for their Centre for Cellular Immunotherapies and the Founding Director of their clinical cell and vaccine production facility. He's a wonderful man and a very special guest because he connects into the very beginnings of CAR T-cell therapy. He was one of the team that founded that therapy and tried it for the first time in patients and, as you'll hear, connects into the Emily Whitehead story that I love to talk about. This is about therapies to cure cancer, and we're going to talk about his backstory as a scientist, we're going to talk about those first patients, and particularly the Emily Whitehead story – who was the first pediatric patient, the first patient to be cured of her acute lymphoblastic leukemia, and the first FDA approved therapy came out of that trial. We're also going to talk about where we're at now, and most importantly for this podcast, all the things we're going to do next, what the future holds with this type of therapy. Now be aware that the audio quality might change a little as we did this remotely, and please settle back and enjoy the podcast …
BRUCE MCCABE: Thank you so much Bruce Levine for coming on the podcast. First of all, it's such a privilege to have you. [laughter]
BRUCE LEVINE: Great to be here.
BRUCE MCCABE: And such a privilege to have your time, because you're also got a personal injury. I understand so you're out of action at home convalescing at the moment. So thank you so much. I would love to start this by just talking a little bit about where you came from and how you got to where you are, whether the science came first, or the medicine – or what the loves were and the passions were that got you to where you are. If we could spend a few minutes on that that'd be a wonderful way to start this.
BRUCE LEVINE: Yeah, sure. So maybe not... So we're romantic to say where I came from is the suburbs and the suburbs. In the age of Apollo and astronauts and great attention on exploration of space and I thought, well, maybe I'll be an astronaut, but that's pretty hard. Only a few people get selected, or maybe I'll be an astronomer because I like to look at pictures of stars and planets, and then I found out that being an astronomer really involves a whole lot of math more than anything. So, that made it less attractive. But my father's a retired scientist, research scientist, and my mother is a retired nurse. So there was science and medicine in the household and that was a lot of my pastime, reading along with National Geographic, and really trying to understand how the world works.
BRUCE MCCABE: Interesting. So very broad. And it gives me hope because I started in physics and then I couldn't handle the maths either. So I switched to computer science and then I'm ending up doing communication related stuff [laughter] but there you go. So, what next? I mean, because you got into immunotherapies. Well, I know you as this leading scientist in immunotherapies. That's how I know you from our visit very recently at the Perelman Institute and our little lab tour that we took. But what steers a pathway to that kind of specialization?
BRUCE LEVINE: Yeah. Well, I think it was facilitated by my parents. And let's skip the teenage years. And I had a great time in overnight camp and I wanted to go the next year. But my parents said, well, maybe not. And my father had a job for me with a colleague of his down the hall at the Wistar Institute. So that's what I did that summer when I was 15. Turning 16. So I learned cell culture, I learned how to make cell culture media, I learned about counting cells. And that was really interesting. And I did that the next summer. And then when I went to college at the University of Pennsylvania, and Wistar is on the Penn campus, I kept that job part-time while I was an undergraduate student. And so I majored in biology, minored in history, and I knew I didn't want to go to medical school and in part, well, the training's so long, and in part, you have to work with sick people and dead bodies and blood and guts and all of that, but still really interested in science. And then logical step would be graduate school, right?
So I talked to my father about that. And he said, well, if you do want to do that, you should work in the lab full-time for two years to be sure that's really what you want to do before you apply to grad school. And it's good to have that experience as well. So that's what I did. I took a job at Children's Hospital of Philadelphia, actually, in the Division of Infectious Diseases. And my job was to do the immune assessment on serum samples from people that were enrolling in clinical trials of the varicella or chickenpox vaccine and the combination MMRV vaccine. So early exposure to clinical trials, to translational work, to working in a hospital. And this lab was in the main building of the hospital. And to get there on the eighth floor, you had to ride the elevator and there were kids there who were patients in wheelchairs or in stretchers. And it really drives home, well, why are you doing the research anyway? So I think that was my first spark of science and of translational and clinical research.
BRUCE MCCABE: Yeah. So the history with the them with Children's Hospital of Philadelphia goes way back to the very beginning. You've had a long tenure there.
BRUCE LEVINE: Yeah, I've been there … That was a stint in the mid '80s. So I applied to grad school and wound up going to Johns Hopkins, in the department of what was then called the department of Immunology and Infectious Diseases. And I specifically chose a laboratory for my thesis work that was in the bone marrow transplantation research labs that was in the hospital. Right? Making this connection between the science and patients and the hospital. And again, to get to the lab, you had to walk past the patient ward. Not through it, but past it. And while doing my thesis work, I was reading papers by a guy named Carl June.
BRUCE MCCABE: Yeah.
BRUCE LEVINE: And so I applied to his laboratory for a postdoctoral fellowship and began working with Carl in 1992.
BRUCE MCCABE: Fantastic. And of course Carl June is one of those characters where, I mean, there's a team right? Where we get to the Emily Whitehead story, where you all were working together on the first introduction of CAR T-cell therapies. So that collaboration began with you in his lab, I guess, years earlier than your, actually, your first patient. Would that be fair?
BRUCE LEVINE: Yeah. So the groundwork was this, I was working on a way to grow T-cells or T lymphocytes outside of the body. And I developed that, it turned out to be a very efficient method. And once Carl saw the data, or maybe he was thinking this anyway, he said, "How would you like to start and run a lab that grows cells from patients in adoptive immunotherapy clinical trials?" And so this was at the Naval Medical Research Institute in Bethesda, and this first trial was in HIV. And we showed the safety and feasibility of this and showed that we could improve immune function and also began collaborations with a small company called Sir Genesis that was developing the very first CAR T-cells. And that was in the late '90s. And then in 1999, we moved up to Penn to begin working cancer and started our preclinical CAR work in cancer in 2004 and we treated the first adults in 2010 and Emily, of course, in 2012.
BRUCE MCCABE: And Emily, from my understanding of our discussion when you kindly let me tour the lab with Tom and Don Siegel, she was the first pediatric patient for a CAR T-cell treatment. Is that right? And also the first one for ALL, Acute lymphoblastic leukemia.
BRUCE LEVINE: Yes.
BRUCE MCCABE: I believe the first FDA approved therapy was hers is that correct? So she really was patient number one in a whole bunch of respects.
BRUCE LEVINE: Yeah. So we started in chronic lymph for leukemia in adults and we treated seven adults. And then we had a close collaborator. Steve Grupp at Children's Hospital of Philadelphia opened up the clinical trial there in pediatric acute lymph for leukemia. And Emily was the first patient, the first kid in the world to receive CAR T-cell therapy.
BRUCE MCCABE: Fantastic. Now I want to get into that story in a second. But just by way of background we met through Tom Whitehead and it's just worth spending a second on this, the intersections of these stories. But the reason you and I met was Tom was connecting some dots and also I was attending an Emily Whitehead Foundation event shortly after. So Tom and Kari Whitehead, are Emily's parents, this first patient of yours. And what a remarkable [chuckle], what a remarkable family. I mean, Tom has spent, ever since you treated his daughter, he's spent so much of his energy in his life trying to ‘pay it forward,’ as he says, through the foundation, and raising money and assisting other children to go through it. It's just incredible, isn't it?
BRUCE LEVINE: Yeah. And I'll tell you how I first met them. Now, we had started when we moved to Penn in 1999, and a number of clinical trials in cancer, most in adults, some in kids. They weren't CAR T trials. And I had made it a habit, especially with the first patient and then some others, to go to the infusion room and to thank the patient for enrolling in our clinical trial because without people enrolling, we're not able to make progress in the development of new medicines. Well, from 1999 until 2012, I'd never gone to see a child infusion. I just felt I wasn't up to it. But with this new trial, chimeric antigen receptor T-cells, I felt it was such a leap from what we were doing that and I'd had experience meeting patients. I felt the time was right to meet the first patient. And I asked Steve Grupp if he thought it would be okay, he checked with the family, said it was. And I went over to meet them and I wasn't sure really what to expect, right? Because you know that the child, whoever the child was, would be in dire straits, because they're coming to this clinical trial because they have no good options. So Emily actually received her cells split up into three fractions. Day one, day two, day three. And I went on day two and walked into the room and there's this little bald 7-year-old in bed and receiving the cells. And there's Tom and Kari. Kari looking on at Emily, concerned like a mother should be. And, but they were so very welcoming of me.
And it just, uh, after meeting them you can get a sense, not a complete sense, but what a special family they are, and after a few minutes, I forget whether it was Tom or Kari said, “Well, why don't you go sit next to Emily on the bed, and we'll take a picture?” And so that was a little taken aback by that but sure, anything I can do for these patients. And, yeah, then we connected after that, when Emily was recovering after her severe cytokine release syndrome, I gave a tour of the lab to Tom and Kari, and the relationship over the past 10 or 11 years is, they just feel like a part of our family. I mean, Carl June, Steve Grupp, and the whole team. And Tom, Kari, and Emily, it's really been a very special relationship that I wasn't expecting.
BRUCE MCCABE: Yeah. Yeah. They're just beautiful. They're heroes to me, because it's the scientists, who are heroes, and as you say, the people who are going to go through this and making those choices are the heroes. Just sensational. It's a very powerful story. And if we kind of outline what happened there, from what I understand, it was really touch and go, because she'd suffered so much, now she goes through his therapy, the therapy is so successful, in a way. It's so aggressively successful against the cancer that it led to all these inflammatory responses and things, right? So you had to deal with... On the fly, you had to deal with that and find ways through that, or she could ... It could have been fatal in another way. Is that a reasonable description of what happened?
BRUCE LEVINE: Yeah. Yeah. And I can set that up with some additional background just to level-set for the audience. What are CAR T-cells? So chimeric antigen receptor T-cells. Chimera is a mythical beast with the body of a lion, head of a goat, tail of a serpent. And in our case, we're making a molecular chimera that is composed of a recognition receptor on the outside of the cell and signaling domains on the inside of the cell.
And basically what we're doing by genetically delivering this chimeric receptor is we're redirecting immune specificity. So normally your immune cells, they don't normally see cancer derived from your own cells, maybe some viral induced cancers. But we're teaching the immune system in this case to recognize cancer. And so we took Emily's cells out of her body, brought them to the lab, genetically modified them, grew them up, tested them, and then delivered them back.
Now, at the time of infusion, she had a whole lot of leukemia everywhere. Blood, bone marrow, kidney, liver, spleen. And so these CAR T-cells, when they encounter that tumor, they become activated, as you say, and they start secreting inflammatory mediators of inflammation. And that had a cascade effect. Now, in Emily's case, she got much sicker than any of the adults that we had previously treated. And she may have been predisposed to that due to her disease burden or due to some other factor. And why do I mention all these details? Well, it comes to being prepared to analyze events that happen that are good, bad, surprising, unexpected. And so this was unexpected in severity. And by day by day, having her serum analyzed in the laboratory, we could look at these mediators of inflammation. One, in particular, was 10 times higher than we had seen in any adult. That was IL-6 or interleukin-6.
Well [chuckle] there's many areas of serendipity, but one is Carl June's daughter has juvenile rheumatoid arthritis. He had been tracking new drugs for JRA, knew that there was an IL-6 receptor blocker, recently FDA approved, communicated to Steve Grupp at Children's Hospital and said, “Check your pharmacy, if they have this drug, tocilizumab, get it and give it to her.”
BRUCE MCCABE: Wow.
BRUCE LEVINE: So Steve Grupp is saying, well, the ICU docs are going to think I'm a cowboy.
[laughter]
BRUCE LEVINE: But even though this is a shot in the dark, let's try it. So they did have it. She was given tocilizumab and within hours, she started recovering. The pediatric intensive care unit nurses said they had never seen anyone so sick recover so rapidly. And so we learned from Emily how to treat this severe cytokine release syndrome, and in fact, the FDA approval of CAR T-cells was with tocilizumab, so it's a co-label, two different companies, Novartis and Roche, and so they each had to agree on this. And it's another remarkable thing of the development of this technology.
BRUCE MCCABE: That's amazing. That's such an amazing part of the story. And just tell me, Bruce, what was the emotional journey like? Because you've gone through that, this dip in her fortunes, and then she climbs out, and then you eventually get to the point where you find there's no cancer cells. I mean, how did all that feel for you personally?
BRUCE LEVINE: Well, I can't imagine what it felt like for Tom and Kari. For us, there's the initial relief at the infusion that it appeared to go okay, and then in the days after, severe cytokine release syndrome, she's in the ICU, not doing well, and then you get really, really worried, for the patient, for the program … because if the first child on a clinical trial dies, it's done. Right? Who's going to touch it after that?
BRUCE MCCABE: Right. Yeah.
BRUCE LEVINE: So we're thinking about this patient, but we're also thinking about the technology program …
BRUCE MCCABE: Yeah. And all the future patients.
BRUCE LEVINE: … the clinical trial, because gene therapy itself has had a rollercoaster history. And then, little by little, as she recovered and discharged from the ICU, and then it was at day 23 after infusion that the clinical team said, well, let's get a bone marrow aspirate, let's see what's going on, and then it comes back, no evidence of leukemia. And so we had some analysis done on that and dot plots showing that, and this is a geeky scientist thing, but that was so striking that I hung it up on my file cabinet like you would hang artwork from your children on the refrigerator. Because it's something that if you drew on a whiteboard your crazy wildest dreams, what could happen, that's what that looked like.
BRUCE MCCABE: Yeah, you had no idea it would be that successful, that effect?
BRUCE LEVINE: Yeah. Yeah.
BRUCE MCCABE: Yeah, amazing. That's just so wonderful. And, wow, we saw Emily the other day, and that was 2012 when all that took place and here she is now as an undergraduate at university, and that must be incredible, just wonderful to see her living her life so fully and richly.
BRUCE LEVINE: Yeah, and there's another serendipitous, and it gives me chills really, because I went to Penn as an undergrad. And so she is living in a dorm that is just literally 100 meters from my freshman dorm, and Tom and Kari sent me a picture of them in the lounge of her dorm, and the window in the background, you can see my freshman dormitory.
[laughter]
BRUCE MCCABE: Talk about serendipity, oh my goodness, yeah, if someone was writing the script, no one would believe it. They would say no, it's too unrealistic.
[laughter]
BRUCE LEVINE: Yeah.
BRUCE MCCABE: That's amazing. I'm so glad we talked about that and just got that in. I mean, how many now, roughly, do you think have been through this around the world? If she's patient number one, pediatric patient number one, yeah, and derivatives of the CAR T-cell treatment, what are we up to now? 11 years on.
BRUCE LEVINE: Yeah, I can tell you, Children's Hospital of Philadelphia crossed the 500 patient mark.
BRUCE MCCABE: 500.
BRUCE LEVINE: All together, kids around the world, I have to believe it's in the low thousands, and then if you look at the adults, because there are approvals in lymphoma, a couple different types of lymphoma and multiple myeloma with a different target, I think between 20,000 and 30,000, maybe close to 30,000 have been treated with the commercially approved CAR T products. Now, that doesn't include clinical trials. That's harder to track because the patient numbers many times are not reported, but yeah, if you count clinical trials and commercial, well over 30,000 around the world.
BRUCE MCCABE: Do you ever sit and think about that? Because as an achievement, this is all branched out of that early work. It's all part of the tree.
BRUCE LEVINE: Yeah. Well I do, and that's amazing, but I also think about what I've heard from different sources, which is, even in the US, only about 20 or 30 percent of patients that could receive CAR T-cell therapy actually do. So, even in the US, there are disparities in geography and income, race, caregiver status, education, and then we think of other parts of the world, right? Low and middle income countries where in most cases there aren't approvals. So, how do we not only innovate, but how do we disseminate our innovations and provide access to all patients who could benefit.
BRUCE MCCABE: Yeah, how do we start to make big impacts on that? Is this all about cost? Is it about education? Is it about getting to the frontline family clinicians and getting them to understand this is an option? What are the axes we've got to work on?
BRUCE LEVINE: Yeah, it's all of that, and it's very complex. So, certainly these therapies are costly. There's different payment models being looked at, installment, pay for performance, and in the long term, especially for children, these therapies are cost-effective, but they are expensive up front.
And if we think about the approvals in blood cancers, what happens when we have an approval in solid cancers, then you multiply the number of patients that could be eligible by 10, and then we get into the problems of scale, because these are complex to manufacture outside of the body. We need expensive reagents and materials and equipment. We need labor, and I've said that there aren't enough humans on earth when we have an approval in solid cancers, so, we have to think in different ways, not only implementing automation and shortening the culture and reducing the cost of manufacture, but I think the only answer on the larger indications will be making CAR T-cells inside the body.
So, how would we do that? Well, one approach would be to deliver the genetic material directly to the body. But there the challenge is, how do you direct it to those T-cells? You need to have a virus or a nanoparticle or maybe something else that is directly targeted to T-cells. And I'm a co-founder of a company that is addressing that, making in vivo CAR T-cells, Capstan Therapeutic, so that's my disclosure.
BRUCE MCCABE: [laughter] Yep.
BRUCE LEVINE: And what if CAR T-cells and the technology that led to the COVID vaccines had a baby? That would be in vivo CAR T-cell. So think of messenger RNA, like in the COVID vaccines, except that messenger RNA codes for a chimeric antigen receptor, instead of spike protein ...
BRUCE MCCABE: Oh my goodness. Yes.
BRUCE LEVINE: Encapsulated with a lipid nanoparticle, like the vaccines. Except now, that lipid nanoparticle with mRNA encoding the CAR, is coated with an antibody that directs it to T-cells. So we're still in preclinical stages, but you can imagine this would be truly off the shelf. Patients wouldn't have to wait for their cells to be removed from their body and the manufacturing and the testing. This could be administered directly. So we have ways to go, but we have some very exciting preclinical results, some of which are being presented this week at a meeting.
BRUCE MCCABE: Okay. Okay. So it sounds very promising, Indeed. And I'm just going to add, recently I had a chat with Kiran Musunuru, who sounds like he is using a very similar method to target the production of LDL cholesterol by gene edits to the liver. Is that true? He’s combining mRNA and then he’s getting that into a – so that's in a lipid nanoparticle to get into the liver cells to do edits there, to basically I think, yeah, in vivo to do all the edits inside the cell, to get it edit itself if you like. So, it's similar, isn't it?
BRUCE LEVINE: Yeah. Yeah. There's a number of developers and companies looking at in vivo genetic therapies. And if you had asked me, say...
BRUCE MCCABE: So exciting.
BRUCE LEVINE: Four years ago, I'd say, well, show me.
BRUCE MCCABE: [laughter]
BRUCE LEVINE: Because I'm skeptic that that could really work. And then I remember distinctly, I was sitting in this chair reading science magazine, opened it up paper from Intellia Therapeutics with lipid nanoparticle delivery to a treat transthyretin amyloidosis, and it worked! In a clinical trial. And there was a dose response. And it's one of those seminal moments when you read about something and there's the data that shows it can be feasible, and it changes your perspective. It's a paradigm shift.
BRUCE MCCABE: Yep. Yeah. Astonishing. It just opens up all these frontiers in medicine. So if we... And I guess that's what I really wanted to get into for the latter half of this talk with you. If we get into the future frontiers, the directions, the promising new directions of this. So one is, we can get the body to start doing the manufacturing. We do things in vivo. So the CAR T-cells, the body is being used in incubator as a factory. We're using that machinery, if you like. So that will also hopefully lower the cost dramatically. And so that's one. And then you mentioned something a bit earlier, because we've been dealing with blood cancers, and we keep talking about solid tumors. So that's another one, isn't it? This transition to solid, using the same principle for solid tumors. Because they come with their own challenges, don't they? Of access to the cells and so forth.
BRUCE LEVINE: Yeah. Soon after the approvals in blood cancers, I don't know if it was the next day or the next week, people started asking, well, when are there going to be approvals in solid tumors?
[laughter]
BRUCE LEVINE: And then it was, why haven't there been more successes in solid tumors? And the answer to it is, it's much more challenging. It's much more challenging finding the right target that is only expressed on tumor and not expressed on healthy tissues, solid tumors. Much more challenging in terms of being immunosuppressive. Then there's the access issue: how do the immune cells get into solid tumors? Blood cancers, it's a single cell suspension, right?
BRUCE MCCABE: Yeah.
BRUCE LEVINE: In blood and bone marrow, solid tumors, you're dealing with a big mass. So you need to get the cells in there, not just tickling the outside, but really in there in significant numbers.
So we do have some progress. There's progress in identifying targets and enhancing potency and in local administration. And one quick example, I'll give to you is in glioblastoma or in Brain cancer. Now, we started a trial years ago, injecting in the blood. And we did find CAR T-cells traffic to the brain, but there is a way of treating glioblastoma. One of the ways is direct injection of drugs to the brain, and there's the installation of a catheter or it's more appropriately called an Ommaya reservoir. So if that's a standard of care for glioblastoma, why not directly inject CAR T-cells? And so we're doing that now and we're seeing some very exciting results that have been submitted for publication. And I hope maybe by the time this podcast is out, or shortly thereafter, that'll be out and available for the public to see.
BRUCE MCCABE: Oh, fantastic, fantastic. Are there other frontiers as well? Like what are you... Yeah. Am I missing sort of some of these things? Because I'm only aware of those so far. Are there other things that people should be aware of as...
BRUCE LEVINE: Yeah.
BRUCE MCCABE: Yeah, new pathways forward, potentially? [laughter]
BRUCE LEVINE: The one that everyone's talking about now is application in autoimmune disease. And there are some very exciting data that came out of Germany showing that if you, using the same targets, CD99 and B-cells in lupus, and seeing some complete remissions in patients with severe lupus. So that group is reporting on more patients in the next few weeks. There are other groups that have treated patients in lupus and other autoimmune disease where there's a B-cell pathology. And there are companies now dedicated to CAR T-cells in autoimmune disease … And we can even think beyond, right?
BRUCE MCCABE: Yeah, yeah.
BRUCE LEVINE: There's preclinical data in aging. I don't know if that will ever happen. But think of the power of this genetic technology. If you have a target, then you can target an immune cell against that target. And it doesn't have to be a chimeric antigen receptor when you're thinking about immune cells. Think of these cells as drug factories. You could use them to deliver other drugs, like bispecific antibodies, where there have been a number of approvals.
BRUCE MCCABE: So there's actually quite a few pathways branching out again. The tree continues to expand. And what about HIV, which you mentioned earlier? Where the early work started, which I did not know. How are we doing there?
BRUCE LEVINE: Yeah, so we started in HIV in the '90s, and we did see some indications of an effect, but that was right around the time that the combination drug therapies came out …
BRUCE MCCABE: Okay.
BRUCE LEVINE: So many patients with HIV went on these drug regimens. And then with undetectable viral load or a hard-to-detect viral reservoir, it's very challenging to show an effect now. You have to have patients go off drugs, which they want to do, by the way, but you need to design those clinical trials carefully, and that's a longer time horizon and more difficult to show the effect. Now, having said that, we've been investigating HIV all along. I think it's been overlooked as far as the capacity for CAR T-cells to have an effect there. And for that matter, in other infectious diseases, not necessarily with CAR T-cells, but there are academic centers and companies looking at creating, through genetic technology or without it, virus-specific T-cells, and that's applicable in the post stem-cell transplant setting because that's a side effect of stem cell transplantation is those patients are susceptible to viral infection. So I would say CAR T-cells are getting headlines, and rightly so, but there's a lot on page 2, 3, and 4 as far as this technology of manipulating the immune system and integrating synthetic biology and genetic modification.
BRUCE MCCABE: Well, let me perhaps close this by asking you a bigger picture. It's always a hard question, but if we take 20 years from now or even 40 years from now, what's the dream? Where do you think we could get to in terms of therapies on this planet?
BRUCE LEVINE: Yeah, I think the dream is that we will have in vivo therapies of many types. We're going to have them soon with sickle cell disease and perhaps some other hemoglobinopathies or benign blood diseases, not cancerous, that is to say. I think we'll see in vivo CAR T-cells, whether that's an autoimmune disease or blood cancers, I can't say at this point. And I think that technology will enable access beyond what we've been able to see so far with these, let's just call it what it is, relatively primitive ways of making cells, right? We look back and … Look back 120 years and what was automobile manufacturing like? It was very labor intensive. And so now it's automated, it's not bespoke, except if you want a high-end Lamborghini. But I think we're going to see improvements in ex vivo manufacturing. We're going to see the in vivo, and maybe combinations with some other therapies that we can't imagine, and, is it too much to think about with 23andMe and genetic diagnostics, people who might be predisposed to a certain disease, to receive some preventive?
BRUCE MCCABE: Yeah.
BRUCE LEVINE: Maybe some of the technologies that we've talked about.
BRUCE MCCABE: Yeah. Wonderful. Absolutely wonderful. And I remember looking at your bio, under all of the long lists of things that you're involved with, with cellular work and immunotherapies, it said under “description of other expertise” you had “good manufacturing practices,” and it comes up a lot, doesn't it? It's about systemizing this inside the body and outside. I kind of chuckled when I saw it because, yeah, Henry Ford! You're also interested in process. Very much so.
BRUCE LEVINE: Yeah. Well, look, I come from an immunology background, but also so manufacturing. And good manufacturing practices are an FDA requirement for all drugs and equivalent systems throughout the world. So it's a system of quality, and it boils down to: “say what you do, do what you say, prove it, and improve it.” Also, documentation, training people. And what I love is integrating the new technologies to the manufacturing and analytics as well.
BRUCE MCCABE: Yeah, yeah. Wonderful. Is there anything else that people should know about? I think we've covered a lot of ground for the pod. We're watching your work closely, but any other messages you'd love a broader audience to be conscious of?
BRUCE LEVINE: Yeah, I always want to close with thanking the patients who enroll on our clinical trials, even if I can't meet them. If the message gets out, without patients enrolling on clinical trials in cancer or any other disease, we're not able to make progress in new medicine. And what goes along with that is understanding what is scientific and clinical validation. That there is oversight by appropriate regulatory bodies. You know, with any new technology there are shady operators, and we have that in cell therapy, people trying to market direct to consumers so-called stem cells or something else, and unfortunately, patients get harmed financially and medically. So it's very important to go to the reputable source and understand the science and the reputation and the approval process, even in a clinical trial situation.
BRUCE MCCABE: Well said. Look, I'm looking forward to watching the next decade unfold with all these new frontiers. So many extraordinary things that are going to do good for the world. But you are a truly extraordinary person, and you've already had a truly extraordinary impact on the world through tens of thousands of patients. So, such a privilege to talk to you, Bruce. I wish you the best of luck, and also I wish you well with your speedy convalescence with your knee injury.
BRUCE LEVINE: Yeah, thanks [laughter]. And you know I also have to say it's very much a team effort. These complex therapies cannot be developed without the expertise of complementary and interlocking teams from the research bench to the manufacturing to the correlative studies to the clinical team. So, behind the development of every CAR T-cell is literally thousands of scientists and clinicians.
BRUCE MCCABE: Well said, Bruce. Thank you so much for your time today.
BRUCE LEVINE: Thank you.
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