Immunotherapy: How the Immune System Conquers Cancer

[00:00:08]so I'm a pretty big nerd but I also like to think I'm pretty social so when you add those two things together it means science pops up in a lot of the conversations I have and before long I'll usually mention immunotherapy and the most common reaction I get is what's that um then I'll say that immunotherapy uses our immune systems to cure cancer and at that point I'll see a lot of people's uh curiosity turn to skepticism and some people ask if it's like an alternative medicine or something and I understand that I mean the idea at first that your immune system cares cancer does sound a little bit like wishful thinking but I assure you that immunotherapy is very real and very legit in fact I'm sure you've already familiar with immunotherapy you've just never heard it called that so basically immunotherapy is just a way to help our immune systems fight disease we've already used it against polio and tuberculosis and small poox and many other diseases we call them vaccines but they're really just a form of immunotherapy um however fighting something that's clearly an outsider like a virus or bacteria is one thing fighting cancer is something else uh it's it's much harder and it's because the disease is much more complex and much more subtle it's our own cells that are rebelling against us above all what makes cancer cancer is its uncontrolled growth but if you look beyond that growth cancer is extremely complex and that's why we're good at treating tumors when they're small before they advance but as they get larger and they progress and they develop new tactics uh our current treatments surgery chemotherapy and radiation don't really work that well which is why cancer still kills one out of every four people in this country luckily we've learned a lot more about both cancer and the immune system we've gotten much better at using immunotherapy to empower patients immune systems and help them to overcome cancer and Conquer it with their own bodies so it was actually uh immunotherapy actually started 125 years ago with a New York City surgeon named William B COI he read about a patient whose neck whose tumors all over his body disappeared after he got a really bad infection and he was intrigued by this connection so he decided that he would purposely infect a patient to try to cure them and crazily enough he actually didn't need any permission for this back then probably wouldn't have gotten it today um but in 1891 he actually treated a man named Zola infected him with bacteria and he had several large tumors including one in his throat that made it so he couldn't even eat and he was near death and although he actually almost died from the infection uh within two days his tumor started to shrink and he soon resumed his normal life Coy and a few other doctors had some successes with col's toxins as they came to call them uh but a lot of doctors didn't really take the approach seriously our technology wasn't that advanced then and the technique didn't really it was hard to replicate uh and beyond anything else we just didn't really know that much about the immune system in fact Coy himself didn't even realize that the immune system was responsible he thought that it was something in his mixture itself that was directly poisoning the cancer cells hence the name toxins so like the pacemaker and a lot of other breakthroughs in the history of medicine immunotherapy also benefited from a little bit of luck in the beginning fortunately for us too while the medical establishment largely largely dismissed CO's work not everybody forgot about it one was his daughter Helen who in 1953 founded the Cancer Research Institute or CRI where I actually work now now in 1953 no one believed in immunotherapy and CRI for several decades was the only organization that actually was devoted to advancing it um and one of one of the we we still actually fund a lot of researchers around the doctors and scientists around the world not only to figure out Bas the basics of the immune system and how it works but more importantly taking that knowledge and then translating into life-saving medicine and probably no one and no one has been more important to immunotherapy or CRI than Lloyd j old here and he actually worked at the same Cancer Center that Dr Coy did which is now called Memorial SLO ketering and and I think it's safe to say that without his contributions Amun thpy definitely wouldn't be where it is today one of the most important things that he uh one of his most important contributions was he helped us figure out how the immune system identifies other cells and it does this by looking at the molecular markers on cells so in in this case it can look it looks at our cells determines if they're healthy or not and then figures out if it needs to do anything about it and the Situation's a lot more complex than this there's a lot more types of markers a lot more types of cells but this is good at capturing the idea that at the root of the immune system's power is its ability to physically interact with and make sense of molecules on other cells um and although you don't really need to pay attention to the colors too much just going forward keep in mind that anything that's red is involved in the immune system's ability to to recognize and then go after the cancer so the way that the immune system does this is actually pretty complicated so I'm just going to cover a few of the basics first we've got General immune cells uh that basically are on Lookout Duty as you can see they don't have any of those red receptors to actually Target the cancer because that's not what they're designed to do but as tumors grow and start to disrupt their surroundings these immune cells are alerted and then they start to do a little Recon and they'll figure out they'll go and they'll interact with Cancer's markers and figure out what it looks like and then after that it can actually coordinate a overall immune response and develop customized cells that are specially designed to Target the cancer now our immune system will normally do this and help protect us but unfortunately tumors often develop ways to protect themselves against the immune system and sometimes the immune system needs a little help which is where immunotherapy comes in so one way that tumors are protected from the immune system is through molecules called checkpoints which you can see here these receptors on the cells um now when these checkpoints get bound they actually act as an off switch and they shut down the immune system C so that they can't attack the cancer anymore luckily we've developed checkpoint or immunotherapy drugs called checkpoint checkpoint blockers that act as a in a sense uh caffeine they help keep the immune system active and awake and so when these checkpoint blockers go in here you can see that they interfere with that receptor and prevent it from being turned off and help the immune system stay on and carry out uh continuing to eliminate the tumor the first checkpoint was actually FDA got FDA approval 5 years ago and since then we've got several more have been approved for several types of cancers and they've helped many patients that were previously untreatable in melanoma which was the first drug first cancer that they were approved for they've actually doubled 5year survival rates already Unfortunately they don't work on all tumors so to tackle these harder to treat tumors we're starting to use the checkpoint immunotherapies in combination with other immunotherapies that I'll be talking about in a little bit and the goal of this is to basically stimul ulate and Empower and enable the immune system to go after cancer we're also realized that some of our old treatments uh also have the ability to stimulate the immune system so we're starting to use those in combination with immunotherapy as well one of these is radiation uh for the longest time we just use radiation to directly kill the cancer cells which is good but more importantly uh when the radiation hits the cells it can cause them to release their markers which will all alert the immune system and allow it to come in and it'll see what the cancer looks like and this allows it to eliminate the rest of the cells that are still there and using radiation in combination with immunotherapy is actually what helped former President Jimmy Carter when his melanoma metastasized to his brain the doctors first Zapped it with radiation and then they added one of those checkpoint blockers that I talked about to give his immune system a little boost and allow it to continue finishing off the cancer another way that we can stimulate the immune system is through viruses just last year actually the FDA approved a modified herpes virus to treat melanoma and they did this this works by uh they first remove the bad genes that cause herpes and replace them with good genes that help the immune system so after these viruses are modified they're injected into the tumors where they infect the cancer cells and then uh the first thing that happens is the cells will start to produce that uh molecule that will recruit the immune system then the cancer cells will die and then when they die they'll release their markers which further stimulates the immune system and allows it to form a strong attack against it we're also developing more personalized immunotherapies and one of these is called car T cells in this doctors take immune cells from the patient and uh then they actually help make them into they transform them into a stronger version that's better at finding and targeting the cancer and there's a number of ways they can do this and we still honestly don't know the best one one of them for example could be uh removing these checkpoint receptors that we know turn the immune cells off and instead replace ing them with the receptors that allow the uh allow the immune cells to go after and Target cancer one person who's already benefited from these is Emily Whitehead uh she was diagnosed with leukemia at the age of five tried a bunch of different types of chemotherapy none of them worked uh but then she got car T cells in 2012 and amazingly they eliminated her leukemia and have allowed her to live a healthy life since then now car cells aren't FDA approved yet but they've been tried and hundreds of patients in clinical trials and in Leukemia and Lymphoma they've worked on about four out of every five patients which is an absolutely incredible success rate um so hopefully I I expect the next couple years we'll start to see some of these become FDA approved and then hopefully more patients can benefit just like Emily has another way that another type of personalized immunotherapy are vaccines now normally when we think of a vaccine we think of something that helps prevent a disease not treat something we already have and while we may eventually be able to develop a vaccine that helps us prevent cancer right now we're focused on using vaccines to help treat people that already have cancer so there's there's many different types of vaccines but above all their job is to uh educate the immune system about what the cancer looks like tell it what the Cancer's markers are and now the reason that these are considered personalized is because every tumor has its own unique mutations so what you tell one patient's immune system won't work for another because the two tumors look different so once you get this information to the immune system again it'll be able to coordinate that that overall response and develop those customized cells that are targeted specifically to that tumor and we still don't know the best way to make a vaccine we don't know what makes the best vaccine either we're still figuring out what's the best information to deliver as well as what's the best way to deliver it um but we are making great progress and we're also starting to figure out ways that we can uh rapidly figure out what mutations a patient has and then convert that into a vaccine seen quickly and for hopefully the most success and I I would these are a bit longer term but I would think within the next decade we'll really start to see some of these succeed as well unfortunately uh both the vaccines and car te cells and the checkpoints by themselves they'll never work for every patient um and because we can we can tell the immune system what to look for and we can give it powerful cells but that's useless unless the immune cells can actually get into the tumor which isn't always possible possible because some recruit cells that act as bouncers and they literally block the immune cells from being able to get in there so these other cells that cancer recruits to support it are a they another level of uh complexity to the whole issue and unfortunately I won't have time to talk about them today I also won't have time to talk about the hundred trillion bacterial cells that live on our skin and in our guts that influence cancer as well as our ability to treat it and not only they they not only ffect cancers of the gut and of the skin but they actually influence our immune system over our entire body so bacteria in your stomach can actually influence cancer anywhere else in your body and tumor the cancer cells and the immune cells also compete so for instance they fight over precious resources in the tumor and if the tumor cells win over the immune cells the immune cells starve and they actually can't do anything else about it um so my slides earlier made it seem fairly simple for us to use the immune system to fight cancer but the environments that tumors create around themselves are extremely complex and there's many factors that control it and those factors also vary from Patient to Patient so what we need isn't a Magic Bullet in fact the Magic Bullets probably doesn't exist um different patient different tumors and different patients uh always need different strategies so rather than a single Magic Bullet what we need are just several great bullets some of which are the immunotherapies I've already been talking about and more importantly we need to know which ones work best against which types of tumors so by designing the treatment specifically for patients based on the characteristics of their individual tumors we can tell the immune system exactly what it we can give the immune system exactly what it needs to be able to go after the cancer we're also making other advances besides the treatments themselves that will benefit patients um as I said earlier if the earlier we detect cancer the better the better the likelihood that we can get rid of it um and we're developing remarkable ways that we can detect cancer earlier so soon you might even be able to get tested for cancer just by a simple blood draw or even a saliva sample um we're also constantly learning more about the immune system which will help us refine and improve our uh our strategies and allow it to really get after cancer unfortunately it's going to take a lot more work before we turn those possibilities into realities luckily a lot more people are starting to get on board in immunotherapies potential and invest in it in just the last year we've had several major groups launched that are focusing on immunotherapy including the Parker Institute for cancer immunotherapy the Bloomberg chemel immunotherapy Institute at John's Hopkins and the cancer moonshot which was launched by Delaware's own Vice President Biden so people always ask me if I think we'll be able to come up with a cure for cancer and honestly a couple years ago I I didn't think we would I thought that Cancer's complexity would be too much for us to came but with the with how far imun therapy has already come in addition to the amazing breakthroughs that I see happening every day I know we're on the right path and even though it may not be possible anytime soon to save every single person from cancer I have great I very strongly believe and more important have great reason to believe that eventually we will be able to conquer this deadly disease [Applause]