by thirty year career and cancer research and treatment that we're beginning to see cured of therapies for diseases that we thought could not even be touched with conventional types of approaches to treatment the words i keep hearing  carty what does that mean carty stands for come eric and engine receptor t cells and that's one of the strategies that we're using to try to develop curative treatments for cancer they all focus on the power of our body's own immune system to fight cancer against the realisation that the new system could be very powerful for fighting cancer just as powerful for fighting infections with viruses with bacteria with parasites we learned at the hutch nearly forty years ago and we were when we were found it is an institution studying bummer transportation that one of the most important parts of the transplant in terms of being curative and it and it is a curative therapy was not chemotherapy or the radiation therapy that was used to treat the cancer leukemia but the donor's immune system is critically important for fighting cancer and keeping it at bay and that's what we've been aiming to do for the last forty years that's why our tagline is cure start here we're not aiming to simply treat cancer we're looking for ways to cure it and these car t cells are one approach for harnessing the immune system and this was developed here by several fantastic investigator stan rebel dr phil greenberg and dr david maloney runs the clinical trials at the seattle cancer care alliance and the way it works stand is just really remarkable when you look at the ten a logical genetically reengineered and reprogrammed to kill the specific cancer that the patient has you first started with this with blood borne cancers like a protein that's expressed on the surface of those cells we taught we educated the t cells using genetic manipulations how to identify those leukemia cells and to destroy them and the results of just been stunning i've never seen anything like this  my entire career where people who had had gone marrow transplantation and relapsed people who had not responded to any of the therapies that we had and had weeks and months to live you take their t cells out reprogram them and reject them i want this is just one infusion no chemo or radiation therapy and their disease just paper eyes and this is truly amazing  manipulate it to the benefit of patients to treat not just blood borne cancers but a very broad spectrum of solid tumors that also don't respond to conventional therapy and the tsunamis in appropriate phrase i think because cancer therapy has that it focuses not on the cancer cell we're not sequencing the cancer cell to find out what the mutations are we're not giving side a toxic treatments that are a little more truck toxic for cancer cells and they are for normal cells but not a lot of the side effects here we're targeting the hosts on immune system all who is trying to activate the human system and we're finding that if you can do that effectively you don't need any of the rest of that virtually all of us have been touched by cancer in some way in our families my  father died of kidney cancer and when i heard you say this is an alternative to conventional therapies you know i'm ready to get up and hug you because the therapies seem to be as bad as the disease that's right and until recently we haven't been able to cure those diseases so the idea that you can take immune cells and move towards that type of therapy is just the type of outcomes just fantastic tell us about fred  founded by dr bill hutchinson who is the brother of fred hutchinson who was a major league baseball player and coach so as far as i know are the only cancer center in the world that's named after a baseball player he unfortunately fred died a young age from cancer which drove his his brother bill to build the institute we focused primarily on cancer therapy and research we have very broadly based researchers and investigators we have the where the center of the largest program for developing vaccines for hiv have a lot of expertise and infectious disease we have a tremendous public health sciences division that's had a major impact on women's health and we have a global presence that includes now a site that we opened and kampala uganda for treatment of cancer in sub saharan africa so we're trying to do our part as a citizen of the international community to help patients that have cancer and just a minute ago when you were talking about  the therapy that you're working on here particular the car t cells there was an excitement i knew i could tell that tells about gary gill and i trained in medicine on the east coast i moved up to boston to train at harvard medical school and dana for cancer institute in one thousand nine hundred four i promised my wife that we've moved back no longer than six years after starting and we stayed there nearly thirty but i was a professor of medicine at harvard and an investigator th medical institute at the time that i started studying cancer which was born in of an experience with a woman young woman with beautiful children a family that died of leukemia that we had to develop better treatments for leukemia and for other types of cancers but at the time i started which was not so long ago we didn't know anything about the genetic basis of the disease we didn't know the mutations that caused cancer is actually very difficult to identify them in those days before the next generation d sequencing technologies came into play we identified dozens of genes that cause cancer some of them were actionable and it was a very exciting time but i realized at some point that in academic environments your you can publish papers and you can clone genes but the question is are you having an impact patient outcome you know had i done something that would make a difference in the life of that woman who died that i took care of back in the one nine hundred eighty s and what i realized and i think this is even more true in retrospect is that the drug development is done extremely well in the pharmaceutical industry and there's often been a bit of a tension between academics and pharma i think actually that's coming together in a way that's mutually beneficial but i want to merck to learn how to make drugs to treat cancer and i learned a huge amount i had an academic hubris that i thought i knew exactly how this worked stand it and many do once you get inside and understand how challenging and difficult it is you have a whole new appreciation for what it takes to take that target that you want to get a drug for and take it all the way through to the f d a to register for treatment of patients my intent and my hope and then to come back into an academic environment to try to bring that insight into these novel therapies that we were developing and at merck i worked on a different type of i mean a therapy that also activates the immune system and was approved by the f d a and nearly record time within three years after the first patient was treated with the drug and realize that this is the time to be at a place like the fred hutch where we can take this longstanding history of interest and expertise and  merit transplantation that dr don thomas and bennett when he was here and see the nobel prize for and convert that into curative therapies for patients that have not just blood borne cancers but a wide variety of solid tumors you have use the word curative a lot what i'm hearing is that it's you know it's not the long term treatment it's a cure so what is what is the patient like after the cure well for patients and my colleagues are  cautious about and judicious about using the word cure at a career in cancer research for thirty years and i've never seen anything like this we've the euphemism that oncologists often use for these types of cancers i was just talking about is that we can treat your cancer but the underpinning of that is we can treat your cancer but we are almost certain we can't cure it those times have changed and i never used to talk about yours for cancer my grandson my papers  any public venues that i was in until just a few years ago when we began to see that happening when i was at work and seeing that happen here at places like the fred hutch and to your question about what happens after the cure in the case of the car t cells cells or infuse there may be side effects sometimes serious side effects that are the consequence of this rapid activation of the immune system is sort of like unleashing a storm in the body that goes out fights these cancer cells causes them to explode so there can be side effects that relate to the efficacy of the treatment what does all that mean those are big words it means basically that there are side effects in the short term your organ systems like your lungs for example with these types of treatments in almost every case those are reversible so it's a matter of getting people through the side effects if they occur and then once that storm h the tumor is gone people go back and have a normal lifestyle and i think the other important point about this is even though we're now treating people only after they've not responded to every therapy that we have because this is new an investigation also want to make sure they get the best standard of care treatment that there are long term side effects from side to toxic chemotherapy can cause secondary cancers that the radiation therapy can do the same thing and there are other side effects that can also involve long term organ dysfunction like all minorities function and one function so what i'm hearing you say is that this approach this carty approach is a replacement for chemotherapy as a replacement for radiation as a replacement for stanek it could be we haven't there's a formal test of that would be to take it right up front and use that as an initial therapy for somebody that has a cute with a blast a quick aiming at we're not quite there yet because we can cure the majority of children at least that have a l l so we would want them to deprive the the curative treatment but we also know the long term sequentially and those children who survive are enormous most of them have heart dysfunction many of them have cognitive  disabilities from being two years old and being treated with cancer therapies they're short in stature because the chemotherapy freezes there are growing bone plates so there are long term consequences and the people who do survive the treatment our hope is that we can bring these carty therapies forward and treat without the long term consequences of the side of toxic agent you know out there right now people who are watching this parents who are watching this  usually i would ask this at the end of the show but i got to ask you right now is when and how do i you know contact fred hutch to see if i can have this for my child well there we have a website that lists contact information for the fred hutch and we'll get this information up on the screen so let's go back then and so let me ask it this way is this a natural progression and the research that has been done over the past thirty years this something completely new that's a great question this is a natural progression and it's a combination of decades of work by investigators here and other centers to understand  together and then engineer it into the fabric of the t cell and able to kill the tumor cells so it's been a a logical progression and i think it's been the dream of investigators in this field for a long time and finally when we got to the point where we could enable the technological advances we're seeing the clinical responses that are so spectacular this is my own cells that you're that you're taking you're not introducing something foreign into my body you're just taking my own cells and helping is so far we've demonstrated this works in a specific type of blood borne cancer the certain type of lymphoid malignancy leukemia as well as some fall as we don't yet know whether this will be effective in treating solid tumors we're working very hard on that as others are but i think there's an open question about the extent to which this will work and solid tumors understanding that we have about a ninety three percent complete response rate and people that have acute lymphoblastic leukaemia is that ninety three percent ninety three percent these are people and that we're dying that literally have weeks or months to live we do know however and this is work that i did it merck that targets the activation of t by in essence turning off the signals that tumor cells provide that turn the teasels off it's a negative of a negative but those types of mechanisms where we give antibodies that take the cell cancers of the sort that your father had just a single agent treatment wow one treatment the in that those instances there are multiple treatments that are given over a period of weeks the investigat trying to understand how long you need to go with the treatment but we anticipate that it's not going to be a lifetime of treatment the way it is for most types of chemotherapy that we use in in research i mean you have a million research for thirty years  this surprise you that that the it's the strength of someone's own human body and their own immune system it does surprise me and i wish i could tell you that i was smarter than i am but i think i was one of many people who  skeptical about this mechanism when you think about how absurd it is to say i'm just going to activate your immune system and it's going to take care of the rest it just seems like that's almost delusional thinking so  i'm not only surprised but i'm stunned by the efficacy of these mechanisms when it comes to these types of cancers and weak when you care for patients that have widely met a static solid tumors you know anything you can to make them comfortable we focus a lot of attention and of life care and comfort for the family how do you want to approach your ultimate demise and death and that's one of the arts of being a medical oncologist this begins to flip that us had a little bit because we can begin to talk with people about ways that we can have an impact that's that we're a lot of work to do it doesn't work on everybody but what about the we're not fully sure and some cases there are seven percent of patients that don't respond that have a l l so we need to understand that we've looked at different possibilities and we're beginning to unravel some of the rationale for why people don't respond initially there are some people who also will relapse it looks in some cases as though that's because the t cells that we cave even though they have the potential of life long in our body sometimes they don't live forever we're trying to understand why that they didn't learn their lesson well enough is that it we didn't educate them properly it's not it's not their fault i think it's our fault yeah exactly immunotherapy that's a that's a bigger thing immunotherapies been around for quite some time it has and that's a very good and those medicines target the t cell itself there off the shelf you don't have to take a person's cells you simply give an antibody that flips the switch on t cell activation but other forms of immunotherapy that are tried and true include naked antibodies there's a drug called right toxin bad for example that can be used to treat the cell malignancies similar to the ones that we're using cortis for if they're not curative but you can put toxins on t antibodies that would be a form of immunotherapy them one that doesn't sound particularly pleasant though because what i'm hearing is that you in order to cure me or in order to treat me are putting toxins in my buddy yeah and that's been the mainstay for  for cancer treatment for all these decades is that we've found drugs that are more toxic for cancer cells and normal cells sometimes marginally more toxic so there are side effects it's the hair loss it's the infections from the lowering of your blood count that and sometimes longer term side effects from those toxic treatments which brings up the question is it worth that's a good question is what you know what would you if you had met a set of cancer would you take any medicine and i think that's an individual decision that in general our our profession is very supportive of providing options for patients and then letting them pursue the course that they want to and there are some circumstances where if you had oily monistat of cancer and you're elderly and infirm and have other side effects or other health care issues you might decide not to before treatment and that's what happens with any technology like this is that you get the first signal on this is a spectacular signal and there's always ways to improve it how do you make sure that everybody responds to you understand resistance and override resistance if the t cells die off in some period of time how do you keep them living longer if they cause too many side effects can you try to dial them down by putting in tuneable genetic codes so that there's a lot of work that we need to do around that but when you have it effect size that so spectacular where you're having a ninety three percent response rate in a patient population whose response rates to anything is going to be close to zero the has been very proactive about trying to move those through the approval pipeline they have an approach that's called breakthrough status where when a drugs identified as having breakthrough potential based on the kinds of results we're talking about even small numbers of patients they'll excel or at the process towards approval understanding that after the drugs approved in the south or for all patients that you need to do a lot more work to understand its safety and its efficacy but this r t has been a cruise or breakthrough drug system understanding how it's both activated and turn down activating it the benefit of cancer patients try to kill terror cells the reverse side of the equation and actually some of the side effects that we see relate to auto immunity that if you over activate the immune system that causes a whole spectrum of diseases that are not well understood in general but they include things like rheumatoid arthritis and crohn's disease psoriasis all sort of collide as scleroderma very challenging diseases to treat there the other side of the equation that's the end in the yang is that auto immunity is your immune system doing too much a nd your body's caught as collateral and there's damage as a consequence of that so if we can amp up the immune system we also have tools that should allow us to have it down and those might be useful for treating auto immune disease individuals can also do something to help our immune systems become healthier and that's not something that i learned in health class when i was in school many years ago is that something that should be be taught i think what you just alluded to that i mean good health practices in general are good for our immune system as it is for the rest of her body i'd also want to be cautious about that there are a lot of homespun remedies out there are some of the commercialised that tout the potential for activating the immune system or for immune health and i'm not saying that they don't work i'm saying that we don't really have evidence that says that there's any one approach that you could take that's going to activate the immune system whether it's a naturalistic medicine or homeopathic approach sure vitamins etc but there's no question though that the person stands a better chance in fighting disease at their immune system is healthy that's absolutely correct you talk about commercialization and the cynical part of me says ok so here we are we've got this wonderful you know potential are we going to see a fight for the money side basically or the pharmaceuticals going to glom in and you know invested in research to help support the process for drug development and they need to stay in business and i'll tell you that that's something that's not done well in academic centers drug development for all kinds of reasons i do think that if you look just a cost effective this though and just think about it from a health care system perspective if you have a medicine where you give one injection and it's curative and balance that against the cost of let's say three years of treatment with chemotherapy radiation therapy which is standard for acute lymphoblastic leukaemia the value proposition just from a health cost effectiveness is very clear it's going to be much much less expensive and the pharmaceutical companies will make a profit  and there's always some debate about whether those treatments that have curative intent are worth one hundred thousand dollars are they worth more than that one recent example that doesn't have to do with cancer was around hepatitis c there's now a treatment that's curative for most patients with hepatitis c which is a huge problem worldwide hundred million hundred eighty million cases worldwide it cost about eighty thousand dollars for that treatment over a period of sixteen weeks there's a lot of complaints about how much the companies that manufacture of that generate for pills basically they don't cost that much to manufacture but if you compare the cost of that to the cost of progressive liver failure cirrhosis liver given for a person's entire life it is even if they ultimately died from complications of their disease if you give one treatment and you cure the disease you know what's the business model or out that and you don't make as much money with those types of drugs and i don't think that matters to the pharmaceutical companies and i can speak for the perspective we had at merck which is that that's not the important thing we'll make enough to make sure that we can subsist but it's not about trying to profiteer even though there's been some debate about that  we only have thirty seconds left what's next for each well we're looking to expand our repertoire and i mean the therapy we have other really interesting and exciting programs for cancer treatment but as it relates to me no therapy to expand beyond party cells and to immune checkpoint regulation we didn't talk about vaccines but therapeutic vaccines may be something that we would want to pursue and most importantly trying to understand the power that we haven't quite got the reins on this horse i mean it's