CAR-T vs AAIT: The Secret Benefits and Risks of Cancer Immunotherapy

Immunotherapy is the future of cancer treatment. But not all immunotherapy is the same. Car T cell therapy has changed outcomes for some blood cancers. But we're going to talk about our approach today called a togless adoptive immunotherapy where we build natural killer cells and dendritic cells specifically for tumors using special messaging. And we'll go into that in a minute. Think of a tumor as a neighborhood and around that tumor, these natural killer cells are trying to get there and they're the police ready to kill the tumor. But around these cancer cells there can be gangs. These are like suppressor cells, these physical barriers that block the police or your immune system from getting in and killing the cancer. And this is the real key to cancer. We're going to get into that. We're going to talk about tumor micro environment. And if those gangs stay in control, the treatments will struggle. The immune system won't be able to do its job. So here's today's roadmap. We're going to talk about car T cell therapy, what it is, any of the side effects. We're going to understand how it works and some of the costs. We're going to go over a toggless adoptive immunotherapy in plain english so we can understand how these natural killer cells and dendritic cells work and how important they can be. And we're also going to talk about how to TR dams damage associated molecular patterns and antigen trafficking. These neoantigens are going to be a big part of the puzzle and I'll make it simple for you to understand. And when there's inflammation and too much blockades from the immune system, it doesn't work well and it can backfire. So that's why not everybody responds. And we're going to talk about what we can do to help people better adapt to care. We'll do a head to head comparison and see when each one fits. I'm Dr. Dino Prado, founder of Envita medical centers. Over the last 25 years, by the grace of God, we've helped patients who've already tried the biggest name, oncology. We've spent decades refining personalized cellular immunotherapies. I remember when I used to work in the lab helping grow cells, measuring targets, tuning the tumor microenvironment and avoiding the one size fits all care. That's what we do and we're going to go into that in this first part. I want to start with the car T cell. So these cells have an Important place. And this is how they work. We take the T cells and they're engineered with the cars. And then those T cells can be now recognized with specific target cluster differentiation 19 for fancy words often shortened as CD19 receptors. So those T cells can recognize specific targets like CD19. Then we grow these cells and they get infused back into the patient. This produces a big win in B cell leukemias and some lymphomas, which is why several products are approved by the FDA to do this work. But where does it struggle? Where are the side effects? A common one is something called cytokine release syndrome. This is a massive storm. You may have heard this during talked about people getting what's called a cytokine storm. Lots of inflammation that is attacking and it's a strong immune effect. So it's an over response of the immune system. And this can cause cell associated neurotoxicity syndrome. And both can be severe and even require for patients to end up in the ICU needing medications and care. They'll need special drugs like steroids or to solumab. And these are like rheumatoid arthritis drugs to kind of calm down that inflammation. So these, this is why the cars can be great car T cells if it can hit the target, but sometimes it can over and get an over response. And that's why, you know, it works for certain cancers with very specific markers. But we don't see it doing the same in solid tumors. So let's go into that. Many solid tumor targets are patchy and they change their antigens all the time. Meaning like the outside of the tumor can shift its antigens like a snake sheds its skin. It can change, mutate, so it makes it hard for your T cells to find it. So the T cells can't always traffic that information. The dendritic cells don't always have the right antigens and the T cells, the natural killer cells can't do their work. So they're do their work, but they can't, they can't get into the tumor because of those neighborhoods that are hostile. Like we talked about these gangs that are blocking the police, your immune system from getting in these car. T cells have problems with them because you can get these massive reactions and you have to calm them down. But sometimes they cause too much inflammation, too much immune evasion, meaning it'll send more cells from the bone marrow, mdscs, myelo derived suppressor cells to block the immune system. You'll have more T regulatory cells. So the NK still can't do their work. So this is the balance. There's an art to the cost of this, probably between manufacturing the cells and hospitalization can be, you know, into the many hundred thousands, really into the early millions million plus to treat a patient. So it's very expensive, but that technology and others will hopefully get better and the cost will come down with the CAR T cells. So the CAR T cell has been a big breakthrough specifically for blood cancers. But it's very restricted because of these single targets. It works well, but it has these intense side effects that can be very strong and they have to be managed in a proper setting and they can be inconsistent for sure when you're dealing with solid tumors. So it's not the ideal path. And you see a lot of hospitals now we do CAR T and it's starting to grow because I have to say there's a huge billable amount. I always talk about the cancer industrial complex and it's here, you know, this is a very high billable hospital procedure care, which means hospitals want to get on board. I'm going to introduce you to another technology we've been using for about 18 years now and perfecting it called the Toggless Adoptive Immunotherapy. This is AIT and it's available through our international facility, this immunotherapy. And so what does it mean? It means we use your own cells, the natural killer cells the Lord gave you. We design them, grow them and we help them, giving them information from stressed material and we help them grow. We give them the right antigens so they can go in and go after tumors. The nice thing is natural killer cells can kill both tumors and viruses. They basically are. They do a great job. They don't need an ID badge for marking. They don't need major histocompatibility complex. It can just go and kill the tumor. So it's really nice when their work and in fact, if your natural killer cells are working you properly, you likely wouldn't have gotten cancer in the first place because it would have gotten rid of it. And this is why, if you will, the immune system is such a key part of cancer treatment. The dendritic cell, which is part of the same treatment. The dendritic cells are the master teachers of your immune system. Think of them as like an alien I said before, where they get their arms out, they grab the antigens and hand them on to the natural killer cells. And then the natural killer cells go and kill the tumors. They teach your immune system what to do. So we load these tumor antigens with new neoantigens patient these neoantigens now teach the T cells to recognize cancer anywhere in the body. And they go after killing them with precision. But how do we teach them? We use specific information. One of the key pieces of information we use is called damps. Damage associated molecular patterns. These damps, they're the body's natural danger signal. And when released at the right amount, they can tell that this dying tumor cells and its information, these tumor fragments are now going out and mature dendritic cells pick them up. And now they can teach the natural killer cell exactly what to do to kill better and faster. So this is the simplicity of it. And so in part of the process that we develop is the way the body would naturally kill the cancer is very much on how we develop the process because that is the steps that we see go wrong in care. So AIT or adopt autoglass adoptive immunotherapy does two things at once. It trains the police, the dendritic cells and it teaches them with the new antigens and it passes that onto the T cells. So now the T cells can go out and kill the tumor and it goes back up to it with special, you know, in an anal it does two things and it can back them up with special units and expand the natural killer cells to take back the neighborhood and go in and kill. So why patients like this approach is because you don't have the side effects you do with car T cell, if any very mild. And it works like your body's natural method of going after the tumor. The reaction sometimes would be just like a fever or heat around the tumor, which are really good signs. And you typically don't get cytokine storms or cytokine release syndrome and neurotoxicity. We just haven't seen that in 18 years at all. But in car TS you do see that because it' very strong and designed with the CAR engineer. Those natural killer cells are going after one specific marker very aggressively. Because those natural killer cells by nature, they're tumor agnostic, they're stress hunters. These dendritic cell vaccines and antigens are also agnostic. And these platforms that we load them with help them achieve their targets. Meaning in a simple language, they can go after any tumor if they have the right information. And that's what they do normally. See, precision oncology and immunotherapy is very different than one size fits all in CAR T cells. I've published on this in team. They can be powerful, but they can have serious adverse events. And you can Be very good if we're going after CD 19 and B cell maturation antigens. But often it's only good for that type of cancer and it can cause strong immunotherapy reactions. So the difference with autoglous adoptive immunotherapy is we use genomics, transcriptomics, immune profiling, spatial biology. This precision like a drone. It's like when you send a drone up in the sky so we can see the tumor microenvironment, we can see exactly what's going on around the tumor and then use tools to change that tumor so it goes from cold to hot. So then the natural killer cells tend to be much more effective when you have cold or you have these gangs blocking the police from getting to the tumor. If you don't remove them, even with car T cell, you just don't get the response you want. This is where precision oncology, I believe has the advantage because we work on that tumor microenvironment first before we grow expand those natural killer cells to do their work. And that's rarely done at all in standard oncology. So how do we design these treatments of your own natural killer cells and dendritic cells, which are called vaccines? It's not a vaccine in the way a vaccine from an infection, but it's like your own immune system has grown and typed to your tumor. We load your dendritic cells with your antigens, which is it's naturally done because that's what these cells love to do. But these are NEO antigens that change over time. And so we tune them using damps, these damage associated molecular patterns and teach them to be strong and go after tumor. Then we expand the natural killer cells and the dendritic cells into large numbers so they're healthy, vibrant, tumor seeking and ready to kill. And then we introduce them into the body at the right dose, depending on the tumor to the cancer cells. So think of it like this, an analogy here of like a snake. Tumors can shed and swap antigens like snakes shed their skin. And the dendritic cell vaccines keep this lesson plan up for the T cells so they can spot the new disguises and they can slowly, virtuously create a cycle that kills the tumor, leads to more antigens, which leads to better teaching, which leads to stronger immunity. And this is the road to long term remission, Killing the cancer, feeding it the new information and repeating it so that your IM system is back on track to doing what it was meant to do in the beginning. That's why immunotherapy is Such a big deal. And so many things can destroy your immune system. Chemotherapy does in high doses. Radiation can affect it. A lot of things can affect it. Infections, chemical toxins, heavy metals that brought on the cancer potentially in the first place. The immune system becomes depressed. And so by changing this, we're reintroducing the body's ability to find and fight that cancer. So let's talk about now side effects between the two. So we have the CAR T cell therapy, which commonly can have the cytokine release syndromes and immune that are associated, that are neurotoxicity syndrome. And so these patients need steroids and rheumatoid arthritis medications and other things to monitor and rescue the patient, sometimes leading to intensive care. That's how dangerous they can be. Prolonged low blood cell counts and risk for infection. That's why early on, back in 2013 when our team was working, we just never moved in the CAR T cell direction because we didn't like those reactions. We felt there was a more elegant and better way to prepare cells. There's a very high cost to them and there's a lot of burden to the patient. With the Toggless adoptive immunotherapy, it's significantly milder, significantly, generally mild side effects such as maybe fever or heat around the tumor, which the immune system is working against the cancer. It means the immune system is working against sickly cancer. And we get no classic cytokine release syndrome or cytokine storms. We don't see neurotoxicity. We really don't see any of that. We see the tumors shrinking and heat, which could be a good sign. That's the most common ones we see. And sometimes you'll get a little pain around the tumor. That's a good sign too because it means it's killing it. So manufacturing also matters when you're talking about natural killer cells or dendritic cells. And most of this is not done in the United States. Now CAR T cells are done because they're approved by the fda. But a lot of these are often in other countries. They're in Latin America, Mexico, Europe and the majority of the places in Latin America and in Mexico, almost all of them that we know of do not use human based cytokine product, which is really important. They're not using human based media to grow the cells. They're using Chinese stuff and animal product, which, which is not a good idea, but it's a lot cheaper and that's why they do that. And I think you still have to follow these high Quality standards whenever you're producing cells, in my opinion, because it's important for the integrity of the cell and the quality of the patient care. So even though AIT is a fraction of the cost of car T cell significantly cheaper, we're still using and have used from the last 18 years only the best media products in the world. So let's talk about when these immunotherapies can backfire because we need to know the good and the bad. So when inflammation drives up, it can backfire. Immunotherapy seems to fire up the immune system, but if it does it too much and in the wrong way, it can lead to the tumor kind of trying to protect itself and releasing more cells in its neighborhood to block the natural killer cells and pushing inflammation and metastases. So how does that happen when the neighborhoods like for example, have certain cells around it, let's say macrophages, immune cells, they can flip after an intense tumor killing and there's lots of debris buildup because you get a lot of tumor die off. With these immunotherapies are so strong you'll get tumor associated macrophages. So too much inflammation can be damag promote the T cells to not be able to do their work effectively and promote tumor growth, invasion, new blood cell development and angiogenesis, which creates more metastases and spread. So I don't want to confuse you, but it goes back to everything has to be done in the right balance, not too much, right at the right target. And there's an art and science to this because immunotherapy is powerful. And one of the ways we avoid this is we use a technique called apheresis. We clean the blood out of this debris so that when we have tumor die off, which we're monitoring very carefully with all our cellular markers and all our laboratory tests, if we see that rise, which is a good thing, means we're killing cancer, we got to clean the blood out. So we use a technique where we attach a machine to the blood. It's an apheresis, cleans it all out and returns the clean, healthy blood back to the patient. And that reduces the burden. And it works really well. And so now we can start cleaning out these debris that are building up from all this tumor die off. Because you're going to get things like myelo derived suppressor cells that promote the blocking of the immune system. They come right from the bone marrow and they block it. We're going to see M2 mass macrophages, FoxP3T regulatory cells that are blocking the natural killer cell. So this is why tumor microenvironment is so important and never talked about. These regulatory T cells can over express and they can cause a block to the natural killer cell in cancer. So T cells can also become exhausted. So if a patient's already done PD1 therapies and has already done chemo and lots of other things, they likely have exhausted T cells that aren't working. And we need to refresh those and help those respond better. Even while we're growing and expanding the T cells and helping the antigens antigens to the T cells so we can limit any risk of relapse. Cytokine releasing syndrome can drive resistance because of all this big cytokine release and suppressive pathways inside the tumor neighborhoods. Teaching the cancer how to hide. So you just have to think about it. As in immunotherapy, you're going to have good targets and if you overshoot those targets and it's not tight, meaning if your tumor is already open, ready for the immune system to come in, it's hot instead of cold. The natural killer cells will come in, kill and remove the tumor beautifully. But if it's cold in is often you over push the immune system which happens if you don't change that tumor microenvironment. You can eventually get inflammation and resistance. So there's an art to this. But one of the things you'll see after you receive these cells is patients might see something called pseudo progression. What does that mean? So it means like the cancer will swell up looking like it's growing, but it's actually not. It's just the inflammation. You're actually seeing all the natural killer cells gorging into the tumor to kill it. And so you'll see something that's pseudo fake progression and that's also followed by a spike in tumor and die off. And then the imaging shows us that the tumor has shrunk or has been eliminated. So this is some of the patterns you'll see in treatment when it's moving in the positive direction. So why not does everybody respond? I just went over it. Sometimes these neighborhoods are blocking. So that's why in the process of AIT, we couple that with a technology we call chemoimmunoprecision injection where you use interventional radiology oncology with 3D imaging to get around and in the tumor to change the tumor microenvironment with targeted customized medicines so that then the natural killers cells have a better opportunity of doing their job. This is the key and this is, I don't know anyone else that does it in this manner because we've been doing this for years. But you need technology to see it. Like I said, we send a drone up in the sky so we can see around that tumor and see all that tumor microenvironment. That's called spatial biology and immunoprofiling. And then based on that we can change the neighborhood. And then that's the right time that the natural killer cells will be able to come in and do their job without having all of that blocking. As we use the analogy, the police can go in and do their work without the gangs blocking them. When we train these cells, we love to use dams. These damage associated molecular patterns are so important in autologous adoptive immunotherapy because it's giving all of this information, antigen signaling, all kinds of data to the natural killer cell so that the tumor cannot be disguised anymore, it's giving it all the information. So the natural killer cell, think of it as like a hunting dog, it can sniff out the tumor now because it has these dams. And the dams provide all the sign for the NK cells to go to work and all the information for the dendritic cells to give to the natural killer cells. So one's the teacher and one's the attack. And the combination of those are working in sync to help you. So you can have a bottleneck in this antigen trafficking where you have really these neoantigens are not being expressed, they're stuck on the tumor or they're mutating. And so the natural killer cells can't do their job. So in cancer, antigen trafficking means how tumor associated antigens and neoantigens move from tumor place within the tumor and how the immun learn the lymphatic system and the lymph nodes and can look at these antigen presenting cells like the dendritic cells. And this critical part for a strong anti tumor response is that all these things are working in concert. Cancer antigens can get trapped in scar tissue or fibrous tissue and stromal barriers, they can down regulate the immune system and suppress those entire neighborhoods with T regulatory cells. And like I've said, myelo derived suppressor cells create an abnormal blood supply, like actually grow more blood supply to spread the cancer. So this is why we need to get to these and treat them. These damage associated molecular patterns are so powerful. In fact, recently there was a new drug approved that's called cytokine 15. And the drug was approved really for bladder cancers and the Goal was to get some of these NK cells to respond. Now, it's just a small piece of the puzzle, but it doesn't match this full concert of developing the immune system like I'm talking about, because for a pharmaceutical company to do this, it is not practical to build, design, customize this to each patient. So it's a lot of work. In fact, most of the companies would rather produce a vial and, you know, make thousands of them a minute and ship the country. But you. You can't do all this work with just one vial. Everybody's different. The neighborhoods around the tumors are different. The way your natural killer cells are responding are different. Their fitness, their strength, their cytotoxicity, all that has to be dialed in. And that's what the key of precision targeted immunotherapy is. So the dendritic cells and the natural killers there's working together the way your body does it naturally with the right signals to kill the cancer and create that virtuous cycle of passing that healthy information along so the immune system can finish the job. With a powerful immune system and the right targeting and the. You can now see there's a big change in patient care and in results because the cancer now begins to respond. And you shut down all of those blockades to the tumor, allowing the natural killer cells to do their job. That's AIT So if you look at them, they're different. CAR T cell is for blood cancers. That's where it's been approved. But for solid tumors, breast, pancreatic, lung, you name it. You know, prostate, colon, you name it, it's AIT that's what it was designed for, to make sure that the proper antigens are loaded and, and given to the body, grown, and then returned with health to you, your own cells. So you're not getting foreign cells, you're getting your own. So that's why, also, you don't get a lot of the reactions you would get with other immunotherapies. And then you teach the body to continue to do the same, and you shift the cycle. That's the fit, that's the difference. So when we talk about CAR T, it's excellent, it's been validated and fantastic for B cell maturation for blood cancers, where it's not very effective as solid tumors. And that's where autoglyce adaptive immunotherapy, in our clinical opinion, is the best AIT and it's ideal when you're using precision targeting to address the cancer from the tumor microenvironment the antigens and getting direct to the tumor so that you can help teach the tumor to attack with these damps, these damage associated molecular patterns, which gives all the strength and difference to the immune system. I hope this was helpful. It helped you understand the difference between CAR T cell therapy and ait. Some of the goods involved, how it works, how the body can respond and the things to overcome like too much attack and inflammation and immunity. So I hope this was help and we address some of the toxicity and some of the benefits so that you can have a greater understanding of cancer immunotherapy. One thing I want to say is I believe this is the future of ending cancer is going to be precision oncology with these types of customized immunotherapies. This is the future. This is where we have such promise in immunotherapy. And we can already see even when a new drug comes out in immunotherapy, it's like a blockbuster drug. And it's a tiny little piece compared to what I'm talking about today, which is the full concert of the immune system. And I think this is the key going forward. I hope this was helpful. May the Lord bless you on your journey to healing.