Dr. Pamela Ohashi, Director of the Immunotherapy Program



Dr. Ohashi: So I'm here to tell you a little bit about immune therapy. I thought I'd just spend a few minutes talking about the immune system because it's not something that not all of us think about every day.

So why is it that we have an immune system and what does it do? So the main function of the immune system is really to protect us from germs and viruses and bacteria. So the immune system keeps us healthy because that's what it does; it just can fight these germs in a very affective way, for the most part. So where is this immune system found in our body? It's actually found in our blood and it's a type of white blood cell that really is important, it's actually many different types of white blood cells that all work together like an orchestra to defend our body against these terms.

As we know, the blood circulates from through our body but, many of these white blood cells actually end up in our lymphnodes, that's where they live. And yet you know when we all get sick, the doctor feels up in your throat and he says "oh you've got swollen glands," what that means your lymphnodes in your immune system is actually firing up, and you can feel the response in your lymphnodes because all of these white blood cells actually start to multiply in order to fight different infections that we get.

So that's where the white blood cells are, and as Paul said, one on the white blood cells that we're interested in is called the T-cell. The T-cell is known to actually be able to kill tumour cells. And that's what we're very interested in understanding: how do we manipulate T-cells and their function? So one thing that is well known as I said is that the T-cells really defend her body against germs, and so what I have here is that our body has billions and billions of different kinds of T-cells. And each one of these T-cells is made genetically-engineered, if you will, to recognize a certain virus. So one T-cell will recognize one part of a virus, another T-cell will recognize our tumour.

So we're endowed with all these billions of different kinds of T-cells. So what I've got here is I'm showing three different T-cells, but basically some of them can recognize viruses and what happens when we get a virus infection is the virus multiplies in our body, but then we get enough T-cell that can attack these viruses and then the body is cured of the disease.

Ok, so what happens in other situations for example, you have a lot of Tcells and what we don't want to happen is that the T cells attack our owntissues and this can happen sometimes in this causes of immune diseases likediabetes so those two desires are actually caused when the T cellsrecognize your own body and cause attack your own body and cause a problembecause these T cells are are killing off your healthy tissue that you get anautoimmune disease and so does megan's claims that block this from happeningand so some of the T cells that can go on if they get activated attack Iran toshoot diseases what the body has done is put up stop signal to block this fromhappening because of course we don't want that to happen so this is anacceptable overactive immune system but the tackle your body turns out to bestopped so you know there are kind of a problem we think about what's happeningin cancer biology so if you have a T-cell but couldn't fight cancerthing about cancer this part of herself so the immune system can do I have beentold I shouldn't attach myself but I know this is a bad thing that'shappening in the body so the immune system tries to attack tumors and itdoes so in in and we've got a lot of evidence for that in terms of as asresearchers we know that happened but these other stop signal that are leftover from this side of the equation then come into playok so there's there's a battle within the body as I mentioned we know the 2001attack the tumor but those others these mechanisms pop up and he stopped singlesare a problemok so that that really kind of blocks immune system from curing our bodiesagainst cancer so what many researches done they've asked the question what howto regulate these stops ago how can we actually stop the stops and they foundthat if they develop drugs that can do this is a very very good response interms of cancer so what's been happening is that there's several drugs thatactually take the brakes off the immune system they take down a stop signal andthen unleashes the power of human response so that it can now fight thecancers ok and there's two drugs once known for your four and five other drugsmade by other companies because people have recognized the power of this kindof strategy so now five companies have develop drugs that targeted differentstops and some of these drugs are called the Fulham a blueprint embolism andthese drugs are now really blockbuster drugs and it's really what theexcitementthat Paul had mentioned that asked the recent a school meeting and so i'm happyto say that in the development of these two drugs a lot of this work has beendone at the Princess Margaret Anderson was two doctors dr. David Hogan DrAnthony Joshua who contributed as a trial that show that these drugs areactually very very effective in melanoma these drugs are now being tested forother cancers because they realize the potential that you just have tounreached the immune response by locking these stop signal now in the future Ithink the things that we have to think about now is approximately thirtypercent of these patients of patients actually can go on and have a goodresponse that means their tumors do progressed and we do see a positiveimpact on survival when patients are treated with these trucks but that theproblem becomes 30 percent of these patients approximately respond and weshould really be evaluating different criteria about response does not respondand this is really I think the way of the future we have to be thinking abouthow to identify those patients and really provide the best personalizedmedicine going forward so I'd like to delve a little bit deeper getting backto these T cells because as I said these drugs are working really well that'sactually only in melanoma non-small cell lung cancer so full of cancers have beentested and we know those drugs work well but there's there's many many otherapproaches to using the immune system to fight cancer and I'd like to talk aboutthat a little bit more so one of the things I'd like to introduce us howthese T cells work and so I've got the three T cells here and the way theyrecognized tumors in the way they recognize viruses through receptor andas paul mentioned this is what tack actually clone he was the first personthis receptor looks like and genetically clone it and and this really what thekey to also opening up the field of immunology so my point but i wanna makeeach of these T cells have a different receptor and these receptors able toengage different things as I was saying something cage tumors and so there's aspecific recognition and I have on the sides to herself and tumor cells expresscertain things that are specially that are found on tumor cells and what we'redoing in immunotherapy is really trying to get this match we want to get the Tcells that recognize tumor cells ok I'm so in my diagram is the one thatrecognizes the chamber stuff and that's really the whole game and just to giveyou an idea of what they actually look like if you look down on microscope thisis how it is so this is what 2000 look like it each one of these clubs youcan't see the back sorry but each one of these lots of actually what it lookslike when you look Devon microscope and this is where the tumor cell looks likewhen we grow it in in in the lab and so they're just a little bit different butthis is so the whole game about immune therapy is really can we make more Tcells to confront the tumor cells because it's really a numbers game to alarge extent to what's going on in the body wise why is the tumor winning inthe end and wise what what can we do to help the immune system fight the tumorone of the things is really to provide more face T cells that can recognize thetumor and so what what one person who has done really he's championed thefield of what we call adoptive t-cell therapy and this person is SteveRosenberg and he's in the stateand what he did was he thought well if we actually just make a lot of thetumors T cells in the lab and given back to the patient that should work and infact it does work for melanoma and the treatment look something like this youstart tumor sample taken to the lab and you put little pieces in in these dishesin the spring colors actually media is a growth period we can grow these T cellsput little tumor samples in here in T cells grow in here we can evaluate whichones are most appropriate for therapy then their expanded in these lots hereand they can be reintroduced back into the patient now what happens on the sideof the patient well something happens here that's made this whole thing workand this is what doctor rosenberg figured that he figured out that youhave to pre-treat the patient to reduce the number of T cells in the patient'sbecause if you're gonna get the whole budget easels there's no space to putthemselves so we're going to treat the patient to reduce the number of T cellsand then give back 200 billion to more fighting T cells but that actually worksso and then you do some support therapy to keep the T cells alive and thepatient and then that's basically the the treatment protocol that he'sidentified that works very well known and in his hands twenty percent of thepatients have been disease free for over five years and severalabout 30% of patients 50% of the patients 20% of disease free for quitesome time thirty percent have a partial response means a lot of the tumorshrinkage and patients going to survive quite a lot so we were very excitedabout this possibility and it's only been trying so the idea was we bringback the technology to Canada and established this and then try this trydifferent patients and including the ones that are having right now it's allvery cancer admits mesothelioma oK so that's something that's we'veestablished really only Canadians can do this we're very excited to be able toprovide this type of trial in Canada we are also teaching other things right nowin Vancouver and Montreal how to get this this protocol and in order to dothat required a team of very very many dedicated nurses clinicians surgeonapologists and so this is really the team that was put together to bring alot of years and we're very happy to say that we have a running and that we canteach other institutions across Canadathe other thing and you might hear about his chimeric antigen receptors and so Ijust want to defend the slide talking about that because this is alsosomething that's very very excitingduring yea in the last few yearsvery successful therapy and it's based on a completely different idea basicallyreceptors that can recognize the tumor you genetically engineered them to putthese receptors in two patients performed he sells you can mix themtogether and then basically the T cells now expressed to receptors and can cango up and kill the tumors so this receptor is called the chimeric antigenreceptor companies have gotten excited about it and and arnelle developing thisas a platform so three different companies are now working together to dothis and this is basically from them this works for the liquid cancers and isbased on completely different recognition system but basically this isthis is how it's working ok so in this case they're getting 88 to 90 percent ofpatients are responding with this particular type there and again fromliquid Kansas only still blood cancer people are exploring whether thestrategy can work for solid cancers but we don't really have the right shape ofthis receptor to right now we don't know what the right target is so this issomething that's very exciting and developed and I think once once industrytakes interested and we know it's really gonna go for it and very very quickly sothat's that's another important reason why he is doing so well for the last fewyears when I leave you with a couple of a fox and paint a picture of I thinkwhat is the next five to 10 years what is the way forward so we know it worksin many different situations butthe reality is I would say three or four looking very good and we know thatthere's many many different types of cancer so there's a lot of work for usto to figure out what's the best type of immune therapeutic strategy for all thedifferent kinds of cancersthe other thing we have to do is figure out how to break down these barriers andso what I shown here is that we we know we want to make a lot of T cells thatcan recognize tumors but we also appreciated in the last 10 years saidthe tumor actually find it back ok so what I have here is the tumor cells butthey have put up all these different barriers and and different mechanismthat actually impact NPD immune response from working and so what we're learningto is what these various look like industry as well as basic research andfigure out how can you name it manipulate these barriers to knock themdown and also get the immune response to work really well so those are the kindsof strategies that were thinking about in the next five years we have to targetthe immune system but we have to also target than the tumor itself and breakdown barriers and again for all the different multiple diseases I just wantto leave you with the impression that we've got a lot of experience under ourbelts we know how to get some tumors to respond but this really still a lot ofwork that we have to do to understand what combination therapies andpersonalized medicine a really good mood this fieldwanted to do was give you an impression also that we don't just do research wewe think broadly in terms of education and and bringing communities together aswell so with that in mind we formed the communion cancer immunotherapyconsortium back in 2008 so this was really before all the hypetherapy going but we figured that we better have a group that things aboutthis regularly so we better have a Canadian group was there was not one inexistence really there's there's many other research oriented groups that meetannually like the Canadian Society of Hematology but there was not one thatreally meant for the sole purpose of moving forward so farcreated this consortium back in 2008 and its we've had an annual meeting in youknow there's really sponsorship participation is grown in our goalreally was to provide a network of collaborators that we could really shareexperiences and so that really has gone very well with this CCIC as a result ofthe skin cancer immunotherapy consortium we've also been asked to be a member ofwhat we call the world to me and they're become so this council now consists ofeighteen different organizations worldwide and our goal is really to actat the global level to bring different initiatives for immune therapy for itand we've done many in the past including identifying hurdles toovercome certain hurdles to move in there before but our most recentinitiative is is this one that I've highlighted in the bottom and we'rewe're planning a symposium in November 2015 and it's called as an internationalsymposium featuring today's innovatortomorrow's leaders and what we felt was really meant that the younger de thepost dog clinical fellows really don't have a form to get together and networkand they get a global level or collaborate on a global level so weinitiated this one's imposing back-to-back with another Symposiumwhich is it sees the podium society's cancer it's the 30th annual meeting andthey wanted to celebrate in a certain way so we thought as part of the worldimmunotherapy Council we wanted to highlight our young trainees so we'rebringing together 18 representatives from all these different organizationswe're bringing the top together to present in the symposium and at thatlevel they will also get to know each other and be able to collaborate on aglobal level and we really think that's going to also help drive differentaspects of immunotherapy I'd like to end I don't what time it is I hope 20minutes just wanted to highlight our our core vision for personalized medicinewhat we really do it the princess margaret is we've been acting inbuilding three different groups that are specialized in the drug development ofvarious different new drugs including the ones that stop this block the stopsignal we have a clinical genomics program where we're looking at differentaspectsthe sequence in patients DNA and how that can give us clues for their numberto meet their program and we think we need aspects of all of these programsreally to come together to really build precision medicine for the pain PrincessMargaret and that's what we're doing we have many many people who are actuallynow engaging in a lot of discussions understanding what patients respond totherapy what's the genetics do we have a certain signature that will give us aclue about which best combination personalized medicine that we can givefor peace so with that I'd like to give a special thanks to all our supportersas well as the Princess Margaret Cancer Foundation