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Cancer biologists, pharmacologists and immunologists have historically communicated little with each other due to different traditions in training and a lack of integrated perspectives on cancer. Immunologists have been oriented mainly to biological therapies and they have tended to have less knowledge of genetics and pharmacology.
Conversely, cancer geneticists and pharmacologists have been oriented mainly toward small molecule therapies and they have tended to have limited understanding of immunology or immune-based therapies (other than perhaps passive therapies, such as antibodies).
Dr Prendergast received his PhD in Molecular Biology from Princeton University. Following postdoctoral work at HHMI and Merck Research Laboratories, he was appointed to the faculty of The Wistar Institute as a Pew Scholar in the Biomedical Sciences.
In 1999, Dr Prendergast became Senior Director of Cancer Research at DuPont Pharmaceuticals. In 2002, his research groups moved from Wistar and DuPont to the Lankenau Institute for Medical Research outside Philadelphia, where he is currently Professor, President and CEO.
In 2010, Dr Prendergast was appointed Editor-in-Chief of Cancer Research, the AACR flagship journal, and the most highly cited journal in the field.
Hello, welcome to Abcam's webinar on Immunochemotherapy: the future of cancer treatment. Today's principal speaker is George Prendergast. George received his PhD in Molecular Biology from Princeton University. Since then he has held several appointments at Lankenau Institute for Medical Research located outside of Philadelphia. George is currently a Professor, President and CEO of the Institute. Additionally, he is the Editor-in-Chief of Cancer Research.
Joining George today will be Karan Sharma, Products Marketing Specialist at Abcam. Karan completed his Biology Degree from Northeastern University in Boston. Before joining Abcam he worked in research labs in Brigham and Women's Hospital, Boston University School of Medicine, and the Massachusetts General Hospital. I will now hand over to George who will start this webinar.
GP: Thank you, Vicky. Good afternoon everyone. My pleasure today to introduce the immunochemotherapy meeting. What I'll do is give you an overview and the background for why this meeting is important, and why you might be interested in attending; and then I'll walk through the different facets with you to give you a little bit more detail of what you are going to hear.
This meeting will be held immediately before the AACR meeting to ease attendance, and those who attend will stay at the same hotels that they would in Philadelphia where the AACR meeting will be conducted. My co-organizers for the meeting are all leaders in the field on the translational and basic sides, myself, along with Guido Kroemer of the University of Paris Descartes, who is also Co-Editor-in-Chief of Oncoimmunology. On the clinical side, Laurence Zitvogel at the Institut Gustave Roussy, also Co-Editor-in-Chief of Oncoimmunology; and our colleague in Florida, Jeffrey Weber, at the Moffitt Cancer Centre. These two clinical leaders, along with the basic scientists, round out was is an organizing committee that will bring you a very robust meeting that will cover not only immunotherapy, but its interface with how chemotherapy is presented to the patient; and what the mixture of these two technologies will bring in the future.
By way of a background, I'd like to give you a little bit of a context. Most people who have approached cancer immunotherapy today have not come from that field, but come from outside. This is a very hot area of the field of research, and it's actually the oldest area of cancer research stemming back to the 1800s where the roots of cancer immunology began with the father of cellular pathology, Rudy Virchow, who first described cancer as an inflammation that was aberrant and present beyond the point at which a wound would heal. Virchow, as you know, was the father of the notion that disease starts in cells, and he was also the man who gave the first idea around cancer as a problem of inflammation and immune system.
Subsequently, later in the 19th century, Paul Ehrlich was the first to annunciate the idea of immune surveillance, that the immune system could control cancer. Some of the early work done by Coley in the US, and others around the world showed that by manipulating the immune system with infectious agents using bacterial toxins, basically, patients could show the effects on the immune system that were correlated with cancer responses; even the eradication of medaesthetic disease in some patients.
So this aspect of cancer is very old, it was joined by other threads and the most dominant, of course, became the thread that led to cancer genetics. The roots of that field in the 1900s came from studies of animal tumor viruses by Rous, tissue culture studies later by Eagle, cytogenetics by Nowell and Hungerford also at the Fox Chase. These studies became dominant eventually, starting around 1980 with the discovery of oncogenes.
I think a big event that is not widely appreciated that separated these two traditions was in the 1970s with the discovery of immunodeficient animals, particularly the nude mouse that could support the growth of human tumors within the mouse. This is a mouse that had an aberrant immune system to that extent, and did not reject the human tissue. These mice were interesting, partly because they don't have a higher incidence of spontaneous cancer on their own, compared to normal mice. The discoverers of these mice thought that was a very important feature, in fact, this became the root of an argument that said the immune system was not important to cancer: you could destroy it in an animal to the degree that it wouldn't reject the human tissue, and it would support the growth of human tumors and this led to the xenograft tradition and discovery of new cancer drugs. The thinking here was that modern cancer researchers could ignore the immune system, and I call that 'the divorce' the separation of cancer genetics which became dominant, of course, in our field starting about 1980.
The cancer immunologists were sort of sent into the wilderness to some degree, and this is a tradition that continued. It was not until really about 2000 when sophisticated knockout mutant animals were made, and it caused what I call 'the remarriage', the realization by the mainstream of the field that immunology is really important and that the immune system is an important suppressor of cancer, maybe one of the most important, if not the most important.
The nature of these experiments were from knockouts of the stat transcription factors that mediate signals from interferons, also interferon knockouts that showed that mice lacking these genes had very high rates of spontaneous cancer. The problem, of course, with the nude mouse is we didn't know about natural killer cells back then, which were still active in nude mice and maintained their normal rates of spontaneous cancer. But it wasn't until 2000 that this remarriage brought the mainstream to the realization that we all have to pay attention to immunology.
Over the last decade, there's been a conceptual synthesis and it comes between the two different worlds that really were brought together in part also by studies of inflammation. So those studying genes realized that in the tissue if inflammatory signals weren't present, these cancer-causing genes were rather impotent. That was a realization that happened, I would say, starting around 2000 and dovetailed nicely with the demonstrations of the immune system as a key suppressor.
So coming from two lines of work: the xenograft tradition, cancer genetics for targeted therapy, we have now modern cancer cell centric therapy maybe added by efforts to get at cancer stem cells today. Then we have host centric therapy that's gotten a lift from the work on angiogenesis, but also more recently in immunology. Putting those two together is where immunochemotherapy comes in, the idea of treating the host immune system plus the existing treatments of chemotherapy and traditional radiotherapy and surgery. This marriage is really what our meeting is about, and why it represents something new that no other meeting handles in the same way that we will.
What exactly is cancer? This is also an old idea that comes anew as a result of some of the new information you will hear about and become familiar with, not only the level of causality, but treatment. Our modern theory today, of course, is that the rogue cells of cancer are created by cancer-inducing molecules and our modern therapies attack those molecules. For example, by attacking the EGF receptor by Erbitux. There is an established trend in attacking the microenvironment, and this is now part of the mainstream and it's been demonstrated most dramatically perhaps clinically by the success of attacking microenvironment in support molecules that have to do with angiogenesis; the attraction of a blood supply by a tumor. So anti-VEGF antibodies such as Avastin do that.
The new emerging idea, of course, which has taken the field by storm I would say in the last three to five years now, is the notion that immune escape licenses outgrowth of rogue cells, that all cancer cells must learn how, somehow evolve the capability to escape the immune system. The therapies that attack escape mechanisms they restore immune control, can be effective. So the first example of this is, of course, anti-CTLA-4 or Yervoy, the antibody that resets the self/non-self tolerance mechanisms in the body to restore what would otherwise be a tolerance, and to move toward an attack on cancer.
Now, the deeper idea in immunology for over 100 years has really been that maybe the clinical phenomenon of cancer is more than just rogue cells, but rather a clinical problem of loss of control. Certainly, by the age of 50, someone like me or even older, as you get into men that are in their sixties and seventies, it's very easy to find prostate cancer. The notion that dormant cancers exist in the elderly subclinical levels that are not found, are only found serendipitously during surgery for unrelated situations. The problem is not so much that you have cancer cells in you, but that your body has lost the ability to manage them and that cancer might arise from the problem of the loss of control. But that's the clinical phenomenon, that's the big idea at the root of immunotherapy. Marrying that to the attack of the rogue cells, which is what modern established trends in our field do, is what immunochemotherapy is all about.
Immune escape, that concept as part of the traits of cancer, popularized by this figure taken from reviews by Hanahan and Weinberg over the years in Cell. This is a new part of the pie, if you like, and in 2000 when Hanahan and Weinberg first published this notion of different traits of cancer that cancer cells must acquire, this was a part of the pie that was missing and they say it wasn't part of the mainstream. By 2010 it had become part of the mainstream and it now appears that many of the mechanisms that license the escape of the immune system are also tied into metastasis invasion, angiogenesis and metabolics. You'll hear more about this cross-talk between these different elements that we had known about it, and they were accepted. With the newer elements that have only been recently accepted, partly because we're learning about the molecular mechanisms' underlying immune escape. That is one of the exciting features of this meeting that you'll begin to hear about. It's part of the immunotherapeutic realm, but how that interface takes place with the other aspects of cancer and how therapy in those features work, that's also a feature that you'll hear about at the meeting.
Now, the theory of how immune escape evolves in the tumor microenvironment has been, if you like, attached as a veneer, a conceptual veneer, a top to dominant theory of cancer which has to do with oncogenesis and the acquisition of mutated or misregulated genes. In that theory of oncogenesis, which is popularized by Bert Vogelstein and others in the late-eighties and early-nineties, the normal cell is transformed to a more cancerous state as a result of the acquisition of genetic mutations. Also epigenetic changes in that cell can transform it.
The immune system which is very sensitive to changes in structure of self can detect those and eliminate them, but, as a result of that selection, given the transformed plastic state of what might be a very small colony that's dynamic and regulated, there is the possibility for evolution as a result of the selective pressure applied by immune surveillance, immune cells. That selection, which is a fundamental aspect of cancer and its main challenge, the selection for resistance, can lead to an equilibrium state where occult tumors may persist in a dynamic form that are, again, regulated but not eliminated.
This equilibrium state has been demonstrated in animals by Bob Schreiber, and it correlates, it's been suggested to the phenomenon of tumor dormancy, a clinical phenomenon that surgeons have noted for years. This was a controversial area itself until the late-1990s when it was shown that cured cancer patients could still sustain cancers in their system that were actually obtained from an organ transplant. So the organ transplant recipient would come down with a cancer, it could be shown genetically that that cancer actually came from the donor, even though the recipient had been cancer-free for 15 years after the transplant. So this notion of an occult tumor that can persist and be present, but not be a clinical problem has been proven in humans as well as in mice now.
With further iteration of selection for immune resistance, various mechanisms that are selected, eventually you might achieve a state known as 'escape' and this would be the state at which the dynamic but dormant tumor then can begin to get on top of the host. Gradually, the see-saw begins to tilt to such a state that it's possible for malignant cells to begin to accumulate and form a clinically-detectable problem, initially locally, but ultimately in a disseminated form. The modifiers and microenvironment are very critical to the late stages of this process. The cross-talk between the setting of the tissue in the host, genes that don't necessarily drive the disease so much as modify its outcome. The bandwidth on the internet information, if you like, as an analogy here. Those modifier genes and the microenvironment in which that tumor arises, especially its immune microenvironment, become the dominant aspects of whether the genes that started the story actually turn out to be that important later.
Inflammation here has also been a field in which there has been a cross-talk, and I think conceptual synthesis between different minds in the field. Again, the inflammatory microenvironment informs, in some cases, what would be a chronic state into an acute state that arises as a cancer. Not all inflammatory lesions, for example, in the GI may arise to become colon cancer or another GI cancer, but some do. It turns out that animal studies suggest some of the genes that are affecting the immune escape are the same as those that are programming the inflammatory state in these chronic inflammations that dictate what becomes a cancer and what remains as a chronically-inflamed but non-cancerous lesion. So the insights we're obtaining from the marriage of immunoediting, this new theory of how immune escape evolves with the more traditional and established model of oncogenesis, are leading us to these deeper insights that immunochemotherapy will take advantage of.
So for those of you who are not in immunology, what is immunotherapy? Put shortly, it's those drugs or actions that would recruit the patients' natural immune system to fight disease. The most traditional immunotherapy of the last century, one of the glories of science, really, vaccination. In a vaccine, and vaccines have been developed for cancer as well, a foreign agent is introduced into the blood.
This would be in the case of a tumor or a tumor antigen, and there are specialized cells that rove the body rather like tourists and take pictures of what they see. They keep that antigen in hand and rove through the bloodstream until they come to a specialized lymphoid organ known as a lymph node, in which lymphoid cells live and this is where you might think of a sort of a family gathering where pictures are shown. Certain cells respond to those very strongly, a specific recognition of an antigen will lead to an activation of cells, T-cells and other kinds of immune, adaptive immune cells, which then can rove into the body and destroy the, carry that foreign antigen, that foreign picture that was shown in vaccination. This has proved to be very effective at managing infectious disease. There has been a great deal of historical effort to manage cancer in this fashion and, of course, these vaccines are given to manage disease while the disease is present, rather than prevent it typically in the history of cancer research, at least.
But considering the principles there in immunotherapy, we've had a cell-based as well as a biologics that add capabilities, so active immunotherapy. That would lead to the generation of T-cell features either by antigen presentation or direct introduction of T-cells that are activated by tumor antigens. We have passive immunotherapy and this has really been where the great success of the immunologic field has been in cancer research: the use of antibodies to attack cancerous molecules.
Finally, we have immunomodulators and these really modify the existing capabilities of the host. An example of this might be an inflammatory modulator such as the COX2 inhibitor. These are not affecting direct the disease pathways, but rather the modifier pathways that influence whether the disease pathway produces an acute or a low-level perhaps subclinical problem. By this manner, the immune system and improved manipulation by therapy, immunotherapy can step on the gas, affect the breaking clutch or drive the steering wheel to direct the immune system in different ways, and change its attitude towards foreignness, or as in the case of cancer antigens, things that are somewhat different but still look much like us. That is partly the challenge for cancer, how do we tell our immunotherapy so that it attacks the foreignness of the tumor, but not so foreign that it attacks the body? That is one of the challenges faced by the modern immunotherapies, and you'll hear about that.
So active immunotherapy has actually been around for over 100 years: I mentioned Coley's work with bacterial toxins, and these have been modernized so that the toxin itself, rather than the bacteria, has now been studied in the last decade or so by many entities, many organizations. How is it that this has been such a poor project? It really has been to the view of many, like myself, that not understanding immune escape was the problem in the failures of active immunotherapy really to attract adherence.
There are patients that respond historically that you've seen, but these have never been converted into large groups that could be convincing, and the trials have tended to have failed, or barely have been able to manage cancer. Partly, that's because the tumor has erected in the host so many barriers, and has escaped the ability of the immune system to modulate and when you're standing on the brink it's very hard to get on the gas. Supported inflammations and T-cell tolerance, treating the tumor as if it was the self, these are the things that have made active immunotherapy fail. So you'll hear a great deal about mechanisms at the meeting that have to do with immune escape, and how we can degrade those mechanisms. Degrade those barriers that the tumor supports and, as a result of that, make a variety of therapies far more effective than they would be ordinarily.
I'm going to now turn - tell you a little bit about the sessions themselves, and some of the speakers. In the Session 1 we're going to hear about some of the most exciting work in the field that has really penetrated in the mainstream, especially in the clinical sphere. This takes advantage of what have been called 'checkpoint' therapies that activate T-cell responses. As many immunologists on the call may know, APC or antigen-presenting cells talk to the immune system, activate T-cell responses in two fashions by showing the antigen in a special context of a molecule called major histocompatibility. To T-cell receptors that are specific for that and, as a result of that engagement, they are potentially activated. Well, if the second signal comes along it stimulates what are called costimulatory receptors. Those two signals can trigger adaptive immune responses.
The checkpoints are really co-regulatory receptors that do not engage the receptor in a positive fashion, but rather in a negative fashion. They tell the T-cell, 'Okay, you saw your antigen, but become tolerant to it, don't become hostile to it'. These immune checkpoint molecules such as CTLA-4 are those that have been attacked by the early therapies, and you're going to hear about CTLA-4 and also another molecule PD1 in the talk. In talks from a variety of clinical leaders, mainly. Jeff Weber who's our chair and Stephen Hodi from Dana-Farber, they will talk a great deal about the effect of the studies of these new checkpoint therapies in melanoma where they were pioneered. We also have from Memorial Sloan Kettering, Jedd Wolchok's group, Charlotte Ariyan will tell us about how the use of existing therapies in isolated limbs, there perfused in melanoma patients and can energize to be far more effective if they are given with checkpoint therapy. We also have a short talk from Abstracts in this very busy part of the field, where there have been approved products in the PD1 antibodies, as well as the CTLA-4 antibodies.
I want to say a little bit more about checkpoint molecules just to point out, again, to give you a better picture of what's going on in this realm where there's so much activity in the field. The antigen-presenting cell providing a specific antigen that a T-cell can recognize in a certain context, that is influenced by positive and negative regulators from signal 2. There's a large variety of these, some of which you may hear from the speakers, especially in Session 2 on T-cell leverage. As I mentioned, a great deal of the work is going to involve a focus on these molecules that are approved as targets for immunotherapy, but we'll also hear about the others that seem to show the same level of excitement in experimental settings where they've been targeted. We're going to hear also about the signals within the T-cell and the antigen-presenting cell that mediate the downstream effects of these cell surface receptors in the context of antigen. So Liz Jaffee is going to talk about how these signals are leveraged by chemotherapy. Klaus Okkenhaug from the Babraham Institute will talk about PI3 kinase, a major cancer target for small molecule therapy. As what might be a very important immunotherapy in the inhibitors that were originally designed to attack cancer cells, they may have utility in actually attacking the tolerant signals in the immune system.
We'll also hear about how adoptive cell therapies, T-cells that are especially engineered here, taking advantage of these kinds of signals, the antigen plus the signal 2 to be engineered in and infused in the patient. So Steffen Walter from Immatics in Germany, and Greg Beatty at the University of Pennsylvania, will talk about T-cell therapies: Greg touching on what are called 'car' T-cell therapies, which have seen a lot of attention from Penn and Memorial Sloan-Kettering and others.
Just to come back to vaccines, in Session 3 you will hear about some of the latest in what is a long history of efforts to engineer a vaccine in cancer patients. This is a kind of traditional active immunotherapy, again, given the patients that typically have the disease, rather than those that don't. So not as a preventive the way we use infectious disease vaccines, but as a treatment. Olivera Finn will speak about peptidyl vaccines and targets for vaccines. Charles Link from NewLink Genetics will talk about a platform known as HyperAcute vaccines. This is an interesting platform that takes advantage of the natural capabilities in the immune system to reject non-primate species' tissues from a human body, and how that can be leveraged to attack cancer. Then we'll have Catherine Wu from the Dana Farber who will talk about how vaccines might be engineered to adjust with what are tumor evolution issues. Of course, whatever you throw at a tumor it will evolve a resistance to, could we fashion vaccines that can move and dodge and weave with the tumor as we throw therapy at it? So Catherine will speak to some of the evolution issues in cancer.
In Session 4 we'll get toward what are more the molecular and cellular signals of immune escape, the targets and markers that have gone from basic studies to invention, to pre-clinical validation, to early-clinical trials. In Session 4 we'll also touch on what is an extremely fascinating area of the field, which is the effects of the microbiome not only in the GI, but other parts of the body as a modifier of cancer susceptibility and chemotherapeutic response. It is no longer a radical idea to imagine that we could modify the microbiome as a way to modify and improve responses, not only to immunotherapy, but chemotherapy as well. Laurence Zitvogel and Romina Goldsmidz at NIH, will both speak on this in mice and in human settings, and the results so far, that have only begun to be published recently, are very striking. This is an area I think that will be very exciting to hear about. We'll also hear about basically whole genome approaches that Kai Wucherpfennig at the Dana Farber and others have taken approaches to try and discover other T-cell targets, they can get into the zone of breaking tolerance to immune escape.
Session 5 will move towards those pathways that are already beginning to receive a great deal of attention in early clinical trials, the danger signals that activate immune cells and this will be presented by Guido Kroemer. He will focus his talk, to some degree, on the ability of optimal chemotherapeutic agents to effect autophagy, self-digestion that is not only important in cancer cells, but also in T-cells. T-cells that are autophagic tend to be tolerized and getting them out of the autophagic mode may be very important to getting them activated, to fight the tumor. Adenosine signals; these are signals given outside the cell in the microenvironment. ATP is degraded to ADP, AMP, eventually adenosine and the receptors on T-cells that recognize those molecules turn out to be important immunomodulatory signals. John Stagg at the Institut du Cancer de Montréal will speak about that realm where there's some exciting possibilities, because of the existing drugs in this area that have been used for other disorders.
Myeloid-derived suppressor cells, a class of myeloid cells that are very potent in suppressing T-cell function, and will be discussed by Dmitry Gabrilovich, a leader from The Wistar Institute here in Philadelphia. I will talk a bit on IDL pathways that have garnered attention this tryptophan catabolic enzyme, which seems to be at the center of many modulatory signals and now has a number of small molecule inhibitors in clinic. So you'll hear the translational features of these escape pathways, and some of the more exciting aspects of the field, I think, come through from the two sessions that you're going to see here.
Finally, we'll have a treat to close the meeting in getting future perspectives from three leaders in the pharmaceutical industry. As many know, the food chain in how you move an idea to an experimental therapy to a product must engage biotech and pharma, because of the huge costs involved in clinical drug development. For that reason, I think it's important for scientists and clinicians at all levels of the process to hear from those who are in the trenches fighting the regulatory wars, and the cost wars. Then trying to figure out and working with their colleagues, how best to apply design trials, what the biomarkers are? We'll hear from Eric Rubin at Merck, Ira Mellman at Genentech and Michael Giordano at Bristol-Myers Squibb. These are companies that have all brought the early phase, checkpoint inhibitors through clinical trials. They hopefully will speak to us about some of the combination therapies that are now happening, their perspective, I think, in how the field may evolve in terms of what's practical and where the directions are from their perspective? I think it's going to be very important and make an interesting close for discussion, as we get the interface between the clinicians, the engineers, the basic scientists, the inventors and the pharmaceutical and biotech gurus.
So in looking at the meeting as a whole, I hope you will find a lot to be excited about. The immunochemotherapy of the future is going to have a lot of parts, a lot of moving parts, it's going to involve the destruction of the rogue tumor cells the way we traditionally have done it with chemotherapy and radiotherapy. But also the way we do it now with targeted therapies that are personalized to the mutations in the cancer, but those will be combined with checkpoint pathway inhibitors, such as Yervoy or the PD1 inhibitors. They will be combined with immunomodulators, such as IDL inhibitors or Adenosine autophagic pathway modifiers. They will be used in cooperation with adoptive cell therapies or vaccines, for example, in receptive patients that receive adjuvant immunochemotherapy vaccination may help keep them out of the woods longer. We'll hear from the vaccine experts about how prophylactic use as well as treatment may be a part of future immunochemotherapy.
So with that, I think there's a lot of optimism for the future, you'll see all the different aspects at this meeting in a way that you might not see it just an immunotherapy or just a basic science, or clinical therapy meeting. I hope you will join us in Philadelphia to enjoy the fourth international conference on immunochemotherapy, and be stimulated for what follows at AACR. I think we have a great setup and a wonderful city to offer, and we look forward to seeing you. This is now the end of my presentation and I will entertain some questions from the participants of the webinar, but before we go to that I'm going to hand off to my colleague at Abcam, Karan Sharma, who will give a short presentation from the sponsor. Karan?
KS: Thank you Professor for such a clear presentation. I'm sure that there'll be plenty of interesting questions at the end. At this time, I would like to take just a few minutes to highlight products and resources that we hope will be of interest, and that can help accelerate your research.
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To help with your research, Abcam has recently launched a collection of interactive pathways designed to help you find products which work together to elucidate your particular pathway. Below are just a few examples of the many interactive cancer pathways that can be found on our website. If you look at the T-cell activation interactive pathway in more detail, you can see the full signal transduction of T-cell activation starting from stimulation of the T-cell receptor by an antigen-presenting cell, all the way to the appropriate immune response. If you would like to focus on a particular protein in the pathway, such as ZAP-70, simply click on the protein in the diagram, this brings up a listing of the current ZAP-70 products in our catalogue that can then be categorized by the product type filter. Abcam has a growing library of resources dedicated to cancer research. To view Abcam's complete collection of interactive pathways, please visit us at www.abcam.com/interactivepathways. To look for protocols, content, webinars and literature please visit us at www.abcam.com/cancer. If you would like more information and resources on the tumor microenvironment, please visit www.abcam.com/tumormicro.
If you would like to learn more or refresh your knowledge on different types of techniques and applications, watch our archive webinars at any time that suits you with our online webinar library. This can be found at www.abcam.com/webinars. Abcam is pleased to announce an upcoming webinar on metabolic regulation of cell death on March 11th, and will be presented by Dr Cristina Muñoz-Pinedo. This webinar will explore the interplay between cell death and metabolism, and explains the mechanisms of cell death during cancer and ischemia. Thank you for your time. I'd now like to pass the talk back to Dr Prendergast who will be happy to answer any questions we've received during this webinar.
GP: Thank you, Karan. I haven't received any questions from the participants today, so I will just wrap up and say thank you to everyone who has tuned in to listen to the presentation; I hope you found it informative. I also want to thank Abcam for their superlative support in helping us bring this very important and special meeting together. I look forward to participating down in Philly myself in April, and to meeting everyone who can attend. Back to you, Vicky.
Thank you. Thank you George and Karan for presenting today, and don't forget you can always continue with this conversation with George in April at the conference. Or if you have any questions about what has been discussed in this webinar or have any technical enquiries, our scientific support team will be very happy to help you and they can be contacted at firstname.lastname@example.org. We hope you have found this webinar informative and useful to your work, and we look forward to welcome you to another webinar in the future. Thank you again for attending, and good luck with your research!