 Welcome everyone. I'm Anika, I'm part of the IG community, and before I talk about our research project, I want to talk about the story. The story of a girl named Anthony Whitehead. Anthony was living a regular life with a healthy girl until when she was just 5 years old, she got diagnosed with cancer. Or specifically, a blood cancer type called acute localacity leukemia. Now, Anthony had to spend her days at the hospital, unlike the health case, right, she couldn't go to school or kindergarten. In the hospital, she went to the chemotherapy. You probably know what chemotherapy is. Chemotherapy is a cancer treatment where drugs are used to fight the cancer. Now, Anthony went to chemotherapy twice. And by the age of 7 years, so 2 years after her diagnosis, she still had cancer and no chemotherapy had worked on her. So, at that point, Dr. Johnson turned out options and sent her home telling her parents that she wouldn't survive. At that point, her parents had nothing to do with her anymore. And they heard about a new type of treatment called cell therapy. Or specifically, CAR T-cell therapy. This therapy had never been tested on a child before and never on a patient with ever to take the cancer. So, they had nothing to lose and it went a long way. And Anthony was cancer-free within weeks. This treatment saved Anthony's life. Today, she's 40 years old and is celebrating 7 years without cancer. Now, you might ask yourself, what is this miraculous treatment? How could it take a life? Even though doctors had no options for it. So, let's have a look at what cancer actually is before we go into the details of the therapy. In cancer, cells grow uncontrollably and outgrow the healthy cells in the body. Now, in Anthony's specific category of cancer, a cute little blast happened to me on a political blast. Where the cells are out through the healthy cells. Little blasts are normally part of the blood. And in leukemia, they grow too much and outgrow healthy cells. There's another big problem with cancer because normally when you have bad and broken cells in the body, your immune system can recognize and destroy the cells. Now, cancer cells have a way to escape the immune system. So, your immune system can't find the cancer cells. How this exactly works would be a 15-minute talk by itself. I don't know if you can go to that. But keep that in mind, because the CAR-T cells in the body would save Anthony's life across this problem by activating the immune system so that he can find the cancer cells. Let's go through the three main step-by-step, CAR-T cell therapy. How it works is that the immune cells are taken out of the patient's body. Then, in the laboratory, these immune cells called T cells are modified so that they can now detect cancer cells. How this works is that a receptor is called chimeric antigen receptor. And this is where the main CAR-T cells comes from. This receptor is added to the cells, and with this receptor, they can now find the cancer cells. So, my cancer cells basically can't escape the immune system anymore. Now, these modified T cells are infused back into the patient's body, and now it can act as the effect of the immune system. Now, as great as this therapy sounds, and as great as this, there are still some problems with it. Because imagine you take living cells and put them into a patient. These cells are tiny as human and expensive to make, and they only work for one patient, because they have to be the patient's only new cells. Imagine they're in the body now, and they want to know, does the treatment work or not? Are the CAR-T cells doing what they should do? How are the CAR-T cells doing in the body? The CAR-T cells will spread in the body wherever there's cancer, wherever there are cancer cells to fight. So, how can we monitor our quality? Until now, you would have to take the CAR-T cells off the body again wherever they are now. You would have to destroy the cells in order to access the inside information and get the information of your cell state. Now, with cell destruction, another problem arises, because now we can't analyze them over a long period of time, because you destroy them and you know them. So, we are coming to our project now. There should be a way to overcome this problem and to analyze how the cells are doing without having to basically take them out and destroy them. There should be a way to analyze cells while keeping them alive. And alive is actually the model of our project. Alive stands for analysis of living cells by physical experts. And what this exactly means when we're doing a life-saving project? Before we're working through this method step by step, let us shortly again summarize the program. The meaningful method allows us to monitor cells without touching them, and without harm them, so we can analyze them over a long period of time. So, let us start from our approach directly after the injection of cartysal cartysal. The cartysal is now in the body and two questions. Are these cartysals alive? How are they functioning? And because we do not want to harm the cell, we cannot touch the cell when it's around it, because touching will be how many are even killing the cell. So, how do we analyze the cells after this step? The good thing is that cells have a kind of communication system. While in this communication system, cells can share information with the surrounding cells. And this information one cell will share with other cells is transferred by so-called vesicles. Vesicles can be mentioned as small particles filled surrounded by memory and filled up with some sort of cells together. If we now have a deeper look into these vesicles, we can see they contain some kind of trash-like damaged proteins but also valuable information for other cells. And because these vesicles are naturally produced by cells and naturally produced all the time, it's a good idea to use this communication mechanism to receive information from the cells. So, we thought, or we are doing, the hijacking of this measurement. Hijacking means that we are reprogramming ourselves, meaning that we put some information into the cell which is specifically loaded into these vesicles, shortly into them. We also add some adapters that load this information specifically into these vesicles. And the information we are loading is not naturally appearing in humans normally. Why are we using a naturally occurring information? Because if you take a natural occurring information and analyze the vesicles in data steps, you cannot be sure if this natural information is from the cell or any other side of the body. Therefore, we are using not naturally occurring information to overcome this problem. So, this was the general overview of our project works. And now, let us shortly summarize this. We are using a naturally occurring communication mechanism, the vesicles, which we can only find out slightly so that the load is not naturally occurring in information. So, I hope you are still interested and want to know more about this because now it's going to be more interesting because we are going deeper into this approach. You might have asked yourself in this general explanation how would the load information specifically into vesicles and what kind of information are they loading? To answer the second question first, the information we are loading is RNA. RNA is a messenger molecule containing some information. And what you can see on the right side of the slide is that RNA can form structures, like here shown as a pathway. So, RNAs can form pathway structures. And these RNA structures can be recognized by RNA-recognizing proteins. RNA-recognizing proteins can tightly bind to these structures and therefore detect the location. So, now it's very easy to load this RNA specifically into our vesicles because we confuse this RNA-recognizing protein to natural and vesicles-occurring proteins, shown in blue. And because this blue protein is by natural mechanisms loaded into the vesicle, we load also the RNA-recognizing protein into the vesicle and therefore also the captured RNA. So, finally, we have our vesicle built up with the natural-occurring vesicular protein, the RNA-recognizing protein, and the information in the RNA we want to get loaded specifically into the vesicle. And now the vesicles are exported out of the cell and can be found in body fuels, for instance in the blood. So, with our method, we could take out the patient's blood, isolate the vesicles out of the blood and analyze the vesicles that contain our information or not. If the vesicles contain our information, we can be quite sure that our cells are still alive. And why we have put so much effort into this project and think that it's worth the work that it really is going to be now by nature. Okay, so, now that we've talked about how it works, let's go back to why we're doing what we're doing. I think I already told you what CAR-T cell therapy as a cell therapy is, so I'm not going to go into that again, we're going to look at cell replacement therapy. There's a small difference between the two. In cell therapy, you use cells that have a function, the body actually does not. So, for our T cell example, we have this chimeric antigen receptor that the body does not actually have, and only with this receptor you can find and kill the cancer cells. Now, in the cell replacement therapy at the end, you simply replace the broken down damage or unfunctional tissue without introducing a new function. So, to look into an example to make this a bit confusing, let's look into better cells. Better cells are cells inside the pancreas that produce insulin, and insulin is a very important molecule for your blood sugar movement. During a disease called diabetes 1, type 1 diabetes, your immune system attacks and kills these better cells, meaning you no longer produce insulin on your own, you no longer manage your blood sugar movement. What you currently have to do about this is that you have to inject insulin, or pumps, or syringes, multiple times a day, very constant, expensive, it's also pretty unpleasant, and cell therapy thought, what is it that you can implant a cell, but then produce insulin again, and you no longer have to do the insulin injection on your own. So, this is what better cells transplant on cells. They're already in use, and they do exactly that. They produce insulin after transplantation. And we have the same problem here as before. We don't want to take the cells back out to check if they're working. We want to check them while they're inside, which is what we want to use to live for. We want these cells to produce vesicles that we can then analyze and check if the better cells actually produce insulin, if they're going to attack the immune system again, and all without taking the cell back out. So that's pretty cool, and we're actually not that far off the sideline. We're testing better cells in our laboratory right now, whether they can produce and load information into these vesicles. But let's look at a more complex and more vision oriented idea. It's emphatic organs. So we're currently in organ transplantation. We have a circuit that leads to organ, and we have a donor that can give you organ weight. But this is currently pretty unbalanced, because we have a lot of people in the organs, and not a lot of donors, because most people need the organs. What we, all the scientists, love is why we produce these organs inside the laboratory, making this whole system much better, much easier. And we think we can help this in two ways. First of all, during growing an organ inside the laboratory, this is a very complex idea, because you have a lot of cell types that have to work with each other, and in the end, if your organ does not look like it does not function the way you want it to, you don't really know why in the first place. So when you're using a live, these cells will produce vesicles, they take it and analyze, and track back the problem by knowing what should be inside the vesicle, and if it's not, and you track back which cell did not do what it was supposed to do, and you fix the problem, this is original for the first part. Now, if you have the functioning organ, and then you transplant it, these cells still produce vesicles. The cool thing is now we can take the vesicle out of the blood, and then check again how the transplant, the organ doing inside the patient, is it functional, is it being attacked by the immune system, which would be a organ rejection, again just all in the blood. So, to summarize what our idea is for the live, we have a packaging system where information is packed into vesicles that are being secreted into the bloodstream, which one then to isolate the vesicles, all of them analyze what the cells do. Application with all of the cell therapy like RT cells, cell-related therapy as beta cells, which we're already working on, and our vision for the future is to revolutionize or impact synthetic organs when they find the hardware thing. So with this, I want to finally thank our sponsors, which is the Alamir and Atom, as well as the Amazon Center Munich, and our industrial sponsors. And thank you for your attention. Here's now ready to take some questions. There's a couple of people with microphones, who will help you. Microphones, where you are. Here, one. Please come to this side. Thank you. That's a good question. We thought of that as well. And currently you're right, since this is a blood cancer, the cells are fighting will also extract these RT cells out of the blood as well. But the goal for RT cells therapy is only to fight blood cancer and in the end also tissue cancer. So that is a different field, because then the cells want to reach the tissue, which then we have to invade, not just the blood cells, not just the blood cells. Okay, there is a question here. Can you use the last two minutes? I'm not sure what this is actually for, but it was really great. Thank you. I just have a question. What's up there? Thank you so much. Do you replace my therapy? So can you just summarize what we have? So if you want to do this, could you guys are just checking the insulin level to see if the replacement therapy worked? Yes. Also good question. The difference is when the insulin level drops, this is already a symptom. So for example, at that point blood sugar rises, you have to immediately do something. That's an acute problem. Over the rest of the analysis, we hope to prevent this by looking at how the cells are doing. If they're doing that, the insulin production will at this point still be fine. So for example, some cells die, the other cells might at this point just produce more insulin and you don't realize there's a problem yet. So over the vesicles, you can detect the problem or we envision the problem to be detected much earlier than over the actual symptom, making more time to treat the patient. So I just read the question because you have a microphone. The question is, do you measure the level of vesicles or how they change? Yes. We would look at markers that we both need to vesicles and the change of either the tendency or the kind of markers inside the vesicles will tell us what the problem or what the current situation is. There was just one front. There's another question here. And then I see there's one in the back. That's the next one. So I'm very good. I want to ask you, are you going to be learning the RNA coding which is used in the receptor? Is this why the complex is this? Or do you think you're just using cells? Sorry. So currently we're, because in the course of the ITAM, we can only do trends and changes in the cell, basically all DNA. We just put DNA fragments that we've changed where basically all the parts are as we want them to be in the cells, and then they will produce the proteins like we do like the DNA fragments, basically. And then I see the question. Yes. I'm going to directly give you more time to insert the fragments of the changed DNA fragments into the genome of the cells so it would not be temporary, but stay here. Thanks. There was a question on the back, and yes, on my right. We don't have to start yet. Okay. Please put it further through your mouth. Yeah, we need other friends. The technology, maybe, would revolutionize the translation system. So, grab on that. My question is not your example of the new genome. So the data source, what is basically the guarantee that the body won't attack the new form of DNA cells? Are the vesicles so much more specific or are they particular? Just to clarify, do you mean is there a difference between our vesicles and the natural vesicles? What was the difference? Did the incident continue from the data source that you talked about? I think the question was that will your new implanted cells somehow different from what we used before? Or they still can be attacked by the new system? Okay, I understand now. So, different points. The first one is what currently is being done to put the better cells into the patient to put them in a different place. This actually works for a long period of time. What also has been a field of research is to pack these better cells into like a package, like a pouch, a membrane pouch, and then they can still produce insulin and the exosomes, and they go through. But there is no actual connection between immune cells and better cells anymore because they're in this membrane now. So now, when using this technology, the immune cells can no longer detect or attack the better cells. Thanks, I think that's a good topic for the next talk, probably, that you should prepare enough. And I think we don't have any more time for questions, unfortunately, but we can ask more in the break. Thank you very much.