Harnessing immune calls to fight cancer - A success story | Bhuvana Ramaswamy | TEDxInnovationDr
URL: https://www.youtube.com/watch?v=UlsvRCc14U4 Video ID: UlsvRCc14U4 ============================================================ thank you thank you so much for giving me this opportunity today to come here and talk to you all and particularly thank you for allowing me to talk about the success story of how your immune cells can be manipulated to to help patients with cancer and how we are saving lives i can tell you i'm even more excited to talk about this not just as a cancer researcher or a breast medical oncologist but i'm also very very very grateful that i can talk about this because i'm someone who's living with cancer because of this immunotherapy and one thing i can tell you unfortunately unfortunately this is not a short story i gotta talk to you in 15 minutes but this is an epic story that spans over 150 years and i'm going to try to talk to you this about this in 15 minutes so spare with me and i have to tell them next slide so next slide please okay so what is this connection between the immune system and and cancer right so we're always talking about this connection now look around you look around you and think about the number of carcinogens you're either breathing in or you're swallowing every day or you're tasting or it's touching your skin or you're feeling it now look at that those are the list of known carcinogens next slide please there are two big slides of just talking to you about the known carcinogens that's there okay and if i have to put out the list of potential other carcinogens i'll be here another hour okay so next slide please so there are so many carcinogens around us but now let's look at the number of cancer patients so in this annually in this whole world the incidence of new cancers is about 17 million okay and how many people are living on this earth right now 7.8 billion people are walking around this earth being exposed to these carcinogens wherever they are living in whatever form and we have only 17 million cases how is that possible what is going on okay next slide please and what is happening when you are either breathing or touching or inhaling these carcinogens right that's what we need to understand what these carcinogens do is that they break your dna they cause dna damage and dna is your genetic code dna is the code that tells your k normal cells to do their job and then if these kind of breaks the misinterpretation of your genetic material if it is not corrected then over time these are going to become rogue cells and instead of going through a normal cell cycle of multiplying and then dying they're going to continue to multiply and there we go can cells keep multiplying they grow and they're going to become a tumor and they're going to become cancerous all right so that's the problem with these carcinogens next slide please what does your immune cell do immune cells are able to recognize these damaged cells and they're able to eliminate that let's think about that a little bit more i could give you an example think of your immune cells as somebody who proofreads okay as an editor so there is all these dna breaks and look at that there is a bunch of jumbled words because your dna genome has to be in a sequence and if the sequence goes away then you're going to get damaged cells you're not going to get effective cells so think of your immune cells are you as proofreaders and they cannot correct these typos and then you have a whole system called dna repair system in your body and it goes and tries to repair these cells okay but what can happen though these damaged cells our potential cancer cells are very smart and what they can do is they can confuse your immune cells and then as you can see that next next slide please they can make it so complex they can make it so complex and camouflage themselves now the immune cells are a bit confused they're not able to unjumble these words now even then you're able to live in an equilibrium some bad cells but a good cells and you're still able to live well so you're kind of living in this environment where you're still doing okay but if this continues to overcome your immune cells then by natural selections these bad cells will continue to grow and there you have next slide please there you go you have an escape but immune escape and you have the cancer okay that's how your immune cells are working every day next slide please so think of your immune system as really your first line of defense think of two words immune surveillance kind of watching out for those bad cells immune editing getting rid of those bad cells and in case in case that they camouflage and overwhelm the system there's going to be immune escape and when that those cells escape that's when you're going to have growth and and development of cancer okay next slide please so we understand how your immune system is fighting and keeping cancer away but now you that have cancer already developed how can you harness and use your own immune cells to fight those cancer cells that is the question right this is not a question in the last 10 years i just want to share with you there that paper there is from late 1800s and early 1900s there was who was considered the father of immunology dr bill coley and he actually did this then he took infected material from other patients which had germs and immune cells and and injected them into patients with bone cancer and actually showed reduction of the cancer all the way back here talking nearly 150 years ago but and the the way he has put together it's taken us of course this long to make it uh more available and we'll talk about that in a minute so these immune cells are what are these immune cells in your body that's your next question it's your white cells it's your lymphocytes and we have this lymphoid organs all of these help us to fight this cancer and just broadly think about how best can you fight you either make these bad cells more visible to your immune cells or you improve your immunity so that it can find those bad cells and clear them right that's a simple principle next slide please this is just to show you the top on that you can't probably see it all that is like in mid-1800s and it's all the way down all of these discoveries over so many people internationally talk about our previous speaker just talked about connection working together that's what's happened internationally all of us working together and next slide please and that put together all of these people these are the number of nobel laureates of course i would never say these are the people that only people who contributed right these are just the tip of the iceberg so many scientists so many people so many people who worked in the lab the undergrads the post graduates so many people who toiled at night and if you look at them diverse group of people from all over the world working in this country in other country countries that's where we got but i want to highlight two people there that you see the names dr allison dr honjo they got the nobel prize for physiology and medicine just recently because they found the negative regulators of immune cells and we're going to talk about that this is the ads that you consistently see on tv about how immunotherapy is changing lives of various patients next slide please so this is again broadly what can we do what is your cancer cell doing it's hiding from your immune cell and how is it doing it's cloaking itself just like you would think like in a tsa a terrorist gets through the checkpoint and that's what it's doing it's trying to get away from your immune cell so we need to get your immune cells close to the cancer cells we then we need to break those bonds so that your immune cells can spew out those juices that can go and kill these cancer cells so principle of immune therapy is that what but it's not that easy to just do that within the milieu of a host of a human being next slide please i want to take a little moment on this because there are different types of immune therapy and you would hear these words broadly they fall into five categories the first one is vaccines and what do we do with vaccines we actually passively give you the immunity we give you the immunity to the patients and they then able to go fight whether it's an infection or cancer cells okay that is one type and then there is cytokines what we do is take those juices you saw those juices those immune spell cells spill on the cancer cells now we can actually inject those cytokines and that's an approved treatment and what is the other option is called adoptive cell therapy where you take the t cells from the patient change it in the lab and make it more you know fighter cells and then give it back to the patient and then the fourth one which is what we're going to spend more time on today are the checkpoint inhibitors these are the ones that are making huge waves saving lives that is to close down the negative regulators of immune cells and then lastly is the virus therapies again you have heard of this oncolytic viruses what do we do so the viruses are interesting you know uh uh creatures so to speak so when they get into the host when they get into the human they incorporate themselves into the rna and they can multiply within the cell so now imagine you give a virus attenuated virus that it's not going to immediately cause you an infection you give it into the tumor it incorporates itself into the tumor and then starts to multiply now your cancer your immune cells can recognize them you know as a virus particle they have to fight it they go and try to kill the virus in the process your tumor cells are killed so these are different types of immune therapy but we're going to hone in on those checkpoint inhibitors next slide please okay so on this side you see three molecules pdl1ctl4 what are those things those are all present in our body all the time they are negative regulators of your immune system why do we need that we need to be careful right so your body sees a bacteria it's a simple bacteria you need a little bit of immune response to kill it that's it you don't want your body to mount an extraordinary response you don't want to take an ak-47 for a simple family squabble well i hope you never take an ak-47 that's a different matter but so you want to have an immune response that is commissioned to the injury so your body has these natural mechanisms to kind of modulate your immune therapy well what does this cancer cell do smart guys right and we need to get rid of them they try to use these negative regulators to protect themselves so now we have to use in a cancer patient stuff that can inhibit the negative regulator so that your t cells can actually go fight them so here you see you've seen that that's what is showing how they break that bond and these are the inhibitors seven drugs that are already approved and being treated uh with base for patients right now next slide please i want you to hone in on this i obviously don't have time to give you all the data which i could we could talk for hours i've taken one example of response to a a checkpoint inhibitor or this immunotherapy in patients with bladder and kidney cancer hone in on those green lines these patients tumor went down but more importantly honed on how long it stayed down so what these immunotherapies are doing those patients who respond respond amazingly well and respond for a long time so we're trying to make this cancer into a chronic disease but don't forget next slide please watch those tumors or patients who did not respond so we have work to do so those tumors are going up we'll come to that okay so these are all the cancers you can read them there are 14 cancers many of them are very very serious cancers lung cancer metastatic melanoma liver cancer kidney cancer breast cancer for all of which right now immunotherapy is approved in various format or other seven drugs approved for 14 different cancers making waves and saving lives and let's see what kind of impact it's having next slide please so if you look at it between 1991 to 2017 we were reducing cancer related mortality by 1.1 just between 2016 to 2017 the mortality has gone down all cause cancer mortality by two point double that now to you two point two percent might seem low but what are we talking about we're talking about millions of patients right when you think globally that's the kind of impact we can have and think about metastatic melanoma one of the worst disease once it becomes metastatic particularly after it goes to the brain and other organs we are saving more lives in those patients we are have increased or decreased their mortality by seven percent between every year every year by 7.7 from 2013 to 17 the one year survival rate of patients with metastatic melanoma went from 42 to 55 within a few years we're saving so many lives with lung cancer which is a very aggressive cancer and also i want to take a moment about those patients with brain cancer brain cancer that spread to the brain which is one of the worst situations these immunotherapy are actually impacting those cells in the brain so really an amazing story next slide please so are we done is it over we're done we've cured cancer absolutely not the door is open the case is not done the case is not over i shared that with you because so many patients even within melanoma even with lung cancer where it works are not responding as well as it's i only talk to you about 14 cancers there are so many cancers for which we need such treatments that will work and work for a longer time who are these patients where it works how do we figure that out and also about toxicity and i want a moment to talk about that so you might think is there no downside because you do get to keep your hair it's not chemo and there's definitely one good thing there but it can as your body is raising the immune cells to fight the cancer cells it can also fight your own cells so someone's thyroid might stop working that pituitary might stop working they might have severe diarrhea so there are autoimmune side effects that we need to address so there are things that we need to do and that is very critical for us next slide please so how are we doing that that's exactly what we're doing at the pelotonia institute of oncology at the james and we're doing this by creating a novel breakthrough treatment for cancer a holistic approach to cancer by bringing in science basic scientists oncologists endocrinologists rheumatologists and really trying to bring people together next slide please and we are going to be impacting prevention treatment and a survivorship and how can we do this i'm going to go back to the theme of this topic we need to connect whom have we got to connect we've got to connect to the stakeholders who are the stakeholders you are all the stakeholders we will not have the pelotonia institute of technology uh sorry institute of even oncology without you all because it was the pelotonia fund you all volunteering there you are all supporting there these donors and the community connecting with them connecting with the patients right but the patient should be willing to go on trials willing to give their tissue willing to give their blood for and without them will be nowhere we need to connect with all the funding agencies we need to connect with the pharma who have to make the drug we need to connect with government officials nci needs to support us and then bring in all the experts and things so because if we connect if we connect well we can create a cancer free world and that is our goal today and every day and we will get there last slide please and i just want to say thank you thank you to all that was truly in a nutshell and i am really grateful my life has been a privilege to be able to take care of patients and do research but i am also gifted i'm it's a gift every day because it is this immunotherapy that's keeping me alive being able to talk to you here today thank you and have a good day good night thank you