Announcement of the Nobel Prize in Physiology or Medicine 2018



ladies and gentlemen I wish you all good morning I'm very welcome to noble forum for the announcement of this year's Nobel Prize in Physiology or medicine so I will first read an announcement in Swedish followed by English and we will down present some background to the price and then open up for questions of course you Bella fashioning the Karolinska Institutet or a dog was lifted at noble facility eller medicine or tortoise and or Don Scarlett de la silla came along James P Alison of task ooh-hoo for the errors of text or cancer by handling human Hamling of mm fish for its bronze mechanism al the Nobel assembly at Karolinska Institutet has today decided toward the 2018 Nobel Prize in Physiology or medicine jointly to James P Allison and tasko hangzhou for their discovery of cancer therapy by inhibition of negative immune regulation here we see the two new laureates James P Allison was born in Alice in Texas in the United States he performed his prize-winning studies at University of California Berkeley and at Memorial sloan-kettering Cancer Center in New York is now active at the University of Texas MD Anderson Cancer Center in Houston tasco hangzhou was born in Kyoto in Japan he performed his prize-winning studies at Kyoto University where he still active I will now leave the word to Professor Klaus Shara member of the Nobel Committee who will describe this year's discovery so please close ladies and gentlemen let us start by a summarizing metaphor it is all about interference with the brakes of our immune system as a means to unleash this defense and harness it to develop treatment of cancer cancer is a common term for many different diseases caused by uncontrolled proliferation and migration of cells eventually cancer cells can spread to distant organs so called metastasis usually leading to death cancer represents a major medical challenge in the global perspective there are three pillars in the treatment of cancer remove it by surgery eliminated by radiation or attack it with drugs that harm the cancer cells treatment has improved considerably during the last 50 years more than two out of three are killed today but note that these are average figures which consider major differences between cancers in different organs between early and advanced disease and also between different countries for many cancers very few patients can be cured every year many millions of people die from cancer so noble types of treatment are desperately needed there has been a huge investment in basic research with the aim to acknowledge as a platform for new therapies one area was of particular interest can immunity be harnessed to attack cancer so let us look at our immune system it protects us from infections it comprises a great diversity of cells and molecules with different functions and they can be found all over the body a fundamental property of the system is its ability to discriminate discriminate between self and non-self and bacteria can be attacked and indeed innovative basic research in tumor immunology during the last 50 years have revealed the number of ways whereby cancer cells can also be recognized as non-self this led to cure of cancer in many mice and also to successful treatment of some patients however it was impossible to develop efficient generalize generalizable therapies for clinical practice clearly an important piece of the puzzle was missing and this is what our loads this year have solved now let us take a closer look at the T cell with the T appearing here and we focus on it in the 80s scientists have discovered t cell receptors that bind to structures recognized as non-self you see the structure as a dot in purple here these structures can be picked up from cancer cells and be presented by so-called antigen presenting cells these cells that recognize something foreign with the receptor as here they get a signal to act but this is not sufficient to get them going additional proteins on the surface of the T cells must also engaged in the decision acting as accelerator or gas pedal they were called Co receptors and the research field around them was termed co-stimulation many researchers contributed and observed that even more molecules were involved but with quite the opposite function the instead worked like breaks and here they are in yellow or at least one of them in yellow and this one is called ctla4 a complicated name but please remember it it will be very important so when you pull the break it tells the T cell to hold back stop Alison was one of the researchers who observed that this molecule works like a brake you can see that it interferes with the accelerator on the T cell now some research team started to explore this to treat autoimmunity but Addison he had an entirely different ID he had developed an antibody to see Taylor for shown in green here and if you block or release the brake with the green antibody and listen reason the consequence should be that the t-cells are Unleashed and become more active and they should now hopefully attack the cancer cells this was the hypothesis and the key experiment was performed in Alice's laboratory at University of California Berkeley over the Christmas in 1994 and the results were spectacular the mouse who had been treated with the antibody the yellow curve were cured from cancer while the control mice developed large tumors this seminal study represents the birth of a new concept for immunotherapy today often refer to as immune checkpoint inhibitor the brake acts in the checkpoint Allison was now eager to apply it for benefit of patients at first there was only limited interest but eventually a small biotech company took on the challenge to produce the human antibody the first step on the long journey a few years later the first clinical trials were started and one comprised 14 patients suffering from metastatic melanoma the pigmented cancer of the skin this picture shows how metastatic melanoma can present on the patient now he started to treat the patients and some of them showed striking responses the tumors shrunk they could even disappear at the patients showed a more modest or no response at all and severe side effects were noted in some patients but the results were positive enough and this started a long series of larger trials conducted by clinical colleagues to cut a long story short in 2011 the treatment was approved for inoperable metastatic Allyson had now established a novel concept for cancer therapy but several questions remained could checkpoint therapy we developed to cure more patients and could it be generalized to other types of cancer studies that would lead in this direction were already ongoing in a laboratory across the Pacific in Japan actually they had been started several years before Alison's key discovery so we crossed the Pacific we go to Japan and we go back in time to the point where Alison had started and you will remember and recognize the t-cell receptor and the accelerator enter our second laureate that gohan you who 1992 discovered a new protein on t-cells which he called P D 1 and P D 1 is shown on jello here on the T cells he did not understand what the molecule was doing but together with his colleagues at Kyoto University he launched an ambitious curiosity driven research program to understand its function several years of research later he could reveal the chain of molecular interactions leading him to conclude that pd-1 also acted as a break just as italy for but in a different manner you step on the brake and the T cells holds back in addition on you had identified the ligand the molecular partner of pd-1 and he found that it was expressed on antigen presenting cells but also on cancer cells and now it became immediately evident to test whether blockade of pd-1 could also be used to unleash these responses against cancer so what happens when you release the brake like this ho news and other groups immediately started to gather evidence for this and here we are looking at one of the studies of melanoma the skin cancer and in this case it is spreading to the liver in mice the control mice on your left develop multiple metastases in their livers while several of the mines had been treated with the antibody to your right had almost no metastases at all in this study on your correctly predicted that the antibody one treatment might complement the antecedent for treatment since the two worked by a different mechanism he also predicted that pd-1 might give less side effects hanno now also turned to the pharmaceutical industry an intensive program started conducted by other clinical scientists mainly in the u.s. again similar or even more dramatic responses were noted not only in melanoma patients and fda approved the anti pd-1 treatment for melanoma in 2014 and for line transfer as well as kidney cancer in 2015 so now we have two treatments available for patients based on immune checkpoint and therapy and today we have even more and it's time I think to look at some results in patients these CT scans are from a patient treated with anti PD one but the illustrate process is seen also with anta's Italy for treatment you can see the tumor log by the red arrow in the lung note how it has shrunk dramatically to your right and it's on its way to disappear at four months after initiation of the treatment but please note also what happened shortly after the treatment had started at two months in the middle the tumor appears to be significantly larger than it was from the beginning but this is not really growth of the cancer it is due to swelling caused by the inflammatory response with many immune cells entering the tumor and this is called serve the progression and is observed quite frequently and it caused confusion initially since other types of cancer treatment usually results in an ended in an immediate response and shrinkage of the tumor let us finally look at an example of compiled results from many patients these girls represent survival of treated patients with a certain type of melanoma and you should note that just a decade ago most patients with advanced disease like this would have died already after two years previous standard therapies resulted in long-term survival for few percent or less and it would have looked like this the curve compares three groups of patients treated with checkpoint inhibition the release of one break seated a forwarding green release of the other break pretty one in blue and release of both in yellow and we can appreciate that both treatments are working and TPD one in a higher proportion of patients than antici today for but please note the combination for more than 60% of the patients are still alive of the three years this is a spectacular advance in the treatment of a solid metastatic tumor and we can expect even better results in the future when these different checkpoint inhibitors will be combined with conventional treatments so in summary Alison's Antonio's discoveries have added a new leader in cancer therapy it represents a completely new principle because unlike the previous strategies it is not based on targeting the cancer cells but rather the brakes the checkpoints of the host immune system the seminal discoveries by the two laureates constitutes prepared ematic shift and the landmark in the fight against cancer thank you very much so if we could have the lights a little brighter here we have some distinguished experts from the Nobel assembly and the Nobel Committee dr. Jonas Berg who is an expert in oncology Ted Smith from the Nobel Committee dr. Anna Waddell the chair of the Nobel Committee and of course Klaus so please if there are any questions here we have hello my name is Farah from China's national Xinhua news agency I've got a question for the experts so this year's medicine award is given to the new cancer treatment so what are the significance of the so word are we saying that the cancer treatment has been cancers has been a huge challenge nowadays for the human being what are the significance for this award this year top so this type of cancer treatment is very interesting because it works in a completely new fashion all previous cancer treatments were essentially directed against the tumor cell but this particular treatment is directed against the immune system and one interesting aspect is that it works on many different types of tumors not only on one particular tumor but on many different types here we have one custom yeah can you please wait for the microphone we okay we'll start with okay let's go okay I have a question about you know James Ellison anti-cat G for therapy I know that another excellent scientists are on Yale University leapin Chen he's also a high highly eligible or Canada for this you know just order let you know the reason that he's not been selected thank you the question was about another scientist who is not given this year's award now let me first say that the devel committee divides the world of the people of the world in two groups the ones that have received the nobel prize in medicine and the ones who have not yet receive it and we'd love to comment on the ones who have received it I prefer to refrain from comments on the others having said that I would like to add that as I tried to imply in this presentation many scientists contribute is to this whole field and if you want to read about the contributions of different scientists many of them very very smart and clever who contributed a lot we refer you to the advanced information that just I think is now out on the noble web where you can read about all the contributions of many other scientists which were also important at least to stand out thank you I'm sufficient access song from green post and China radio I just like to ask you that when we talk about this immune checkpoint therapy is it it means that doesn't mean that it is a method that narrow down the point to check for the cancer treatment or how better is it is than the previous ones thank you the effects of these checkpoint inhibitors are quite remarkable because they really define a new concept where you release the brakes previous types of immune therapy they were really trying to make use of the immune system by stimulating it and enhancing its capacity but here in that concept you didn't release the brakes and for that reason those therapies were not as successful as these therapies and the fundamental thing also is that these therapies as we are discussing today they are apparently and very nicely working in previously quite therapy resistant tumors as mentioned here malignant melanoma different types of lung cancer to some extent renal cancers to give some examples while quote-unquote simpler cancer which have been sensitive to endocrine therapy cytostatics radiotherapy etc the effect by the conventional therapy has been quite good but for the tumors I mentioned that present armamentarium up until they have not been that fantastic yeah what what about the side effects the side effects are there it's correct but if you compare with other approved drugs or therapies for cancer there by all means always side effects and if I compare their momentary on with the new drugs we are discussing the checkpoint inhibitors the side effects are for almost all patient manageable although they are in a scale up to five they are not rare with grade three to four side effects but mostly of them they are reversible and it's clearly so if you look at the benefit namely the effect on the cancer and then your balance then versus the risk there is no question that there is a clearly positive benefit risk balance for these for the therapy of the cancers we have discussed here this is for Nordic Chinese times I will question for we I would like to thank you for this to great scientists but we have now run thousands for clinical trial with pd-1 and sitio for and with combination therapy so we even run out of patience so what's what's the next future or rational design for this combination with this kick point therapy thank you yes I think what's most promising now we have we have now a completely new tool to add to the toolbox so it has sort of revitalized the whole area so to find the right combination for the right subgroups and even for the right patients and go into a more individualized therapy will be a very important process there are very many studies of course ongoing doing that so there will be more concepts more checkpoint inhibitors most likely but combining what we already have also with conventional therapy there is a huge benefit to gain there I'm sure you the powerfulness by combine therapy I can mention triple negative breast cancer in a small randomized phase 2 study if you just give chemotherapy and 20% one in five patient that tumor totally disappeared in the areas which were there before therapy if you do the combination of chemotherapy plus a checkpoint inhibitor in in six out of ten – after three patients in reality the tumor disappeared so it was a dramatically improvement from twenty to sixty percent in this very early study demonstrating that combination for some patient could be quite useful using the conventional therapy strategies we saw earlier photo of you speaking on the phone to the winners could you tell us a little bit how they reacted when they heard the news that they were this year's winners dr hangzhou sounded extremely pleased a little bit difficult time to guess if we had some expectancy of this news but he seemed rather surprised he expressed very clearly how satisfied he was also sharing the prize are there any other questions I think then if there is no one else want to ask anything that we can conclude this press conference and there are some of you who asked for interviews so we will try and satisfy all requests as quickly as we can so thank you very much for coming thanks [Applause] I was wise professor class seller member of the bail committee we have just heard that this is this year you are awarding the discovery of checkpoint inhibitors could you please explain what this is well first of all this is a treatment against cancer and it's a new principle for treatment because unlike previous treatments where you target the cancer cell this treatment targets the hosts immune system the patient's immune system and it does so by releasing or blocking the brakes of the immune system and when you release the brakes please go faster and we have a strong response against the patient's cancer cells the laureates name's James Ellison he has been mentioned there for a quite a while how come with this you are awarded time is ripe the first approved the drug based on these treatments it came in 2011 patients have been treated for several years now and we can see the long term outcome and it's very convincing and we possibly really big step in the fight against cancer it was quite complicated different cells and different receptors but in order to describe this price in an accessible way what kind of metaphor would you use I would like to use the break metaphor the brake pedal that you have in a car for example where you can step on it and everything stops sit and you get things going this is a new one kind of cancer treatment what cancer patients can be treated using this method are there any limits but the most dramatic responses are seen with the particular type of skin cancer malignant melanoma I'm sure most viewers know what it is it's a pigmented cancer on the skin other cancers that respond with at least a PD one treatment or nine cancer and kidney cancer and lymphoma and many other cancers actually also so it will be very exciting to see in the future exactly how broad how broadly this can be applied personally what makes you enthusiastic by this price I myself am an immunologist and I have actually interesting new discoveries in tumor immunology where we reveal basic mechanisms but they were never sufficient to be able to cure cancer in patients they were sufficient to cure cancer in mice which is somewhat easier and all the other previous attempts to boost immune system such as vaccination or giving cells they worked in some patients but you could never generalize it to many patients and this is what is different about this one and it makes a big difference for certain patients some patients survive and are killed and some patients get four years rather than one year and that is quite amazing no he turned to the laureates in James Ellison and tasuku Pandu who are they I have met them but I don't know either of them very well but the professor allison is a basic immunology sort trained in medicine but in biology from the beginning he became interested already when he was a small boy and his father came in as a chemistry kid and yes at the standard career in basic immunology he made many important discoveries before this one and he has been in many different centers in the United States Berkeley was mentioned here but he has also been at the Memorial sloan-kettering Cancer Center in New York and in MD Anderson in Texas where he is now I'm also told that he plays the harmonica in a blow span because the segments the professor homeo is also very distinguished the basic immunology see section an MD so it says medicine cranium but he has also contributed very important discoveries in basic immunology before this one and he was not in cancer immunology from the beginning similar to demon is a new supporting cast immunology but this basic scientists made the discoveries and persistently followed them through and developed this fantastic treatment stem I'm not sure whether a professor from your place an instrument but I know that he plays good and is very interested in office when they were doing this discovery whether looking for this or was it a surprise for them when they for professor Allison I think he was working with the basic regulation of the immune system like many others and he did not discover the molecule that he was working but he realized its potential so he rapidly tested an ID that nobody else tested I don't know how expected it was for him to get into cancer but he did because Vanya I'm sure he did not think of cancer at all in the beginning when he looked and found his molecules he was two completely different things and actually probably had ideas that it was doing something completely different but as he went on and he gradually revealed how this miracle world he understood with inspiration for medicine how this one could add even more efficiently and finally if you were to do an elevator pitch on this price with the goal to simply convey the overall concept in an exciting way what would you say them these scientists have discovered how you can lock the brakes of the immune system so that it goes much faster and act in a much more intensive way and thus can attack cancer cells so we can kill cancer with you

32 comments

  1. Well deserved, but there should be more of these prizes. For instance, why have Stewart Adams, and the rest of the team that developed Ibuprofen, not won the Nobel prize?
    Just imagine all the pain they have relieved! Maybe they should have a Nobel prize for medicine every month. This would keep what's really important in people's minds every month, rather than just once a year.

  2. Wow this is exciting! I just finished learning about immunology at A level this has got me even more excited about our immune system. Congratulations to the winners!

  3. Thank them for not giving up on immunotherapy, which was apparently dismissed decades ago. If you look at Dr Allison's publications he's been spending a lot of time on cancer immunotherapy specifically

  4. The one who asked about the other LI CHEN something… is it because he is Chinese and you are also and that is why you have asked!

  5. Congratulations to all of you and also Thank your colleagues to helping and support you for your wonderful work. Go ahead

  6. They both deserve it, they started the research area of cancer immunotherapy and their discoveries have led to the development of many drugs targeting different types of cancers lastly a new one approved by FDA for cutaneous squamous cell carcinoma. They are great men with great minds.

  7. just amazing and a realy breakthrough in cancer therapy.. it has the advantage of being more specific against the harmful cells only not in rondom way just like previous lines of ttt it looks like the revolution of antibiotic to a large extent

  8. Congratulations to both Dr. James P. Allison and Tasuku Honjo, Thank you so much for your amazing work done in the field of Immunology.

  9. We live in a region where the great work of these two physiologist may reach within upcoming 50 years or more. I am not saying this because of I am a person without hope but conditions here are so severe that 1 to 2 person die every year in a very small village of population less than 1K infected by cancer. The reason behind this is unaffordable medicinal therepy of cancer. Is not there any instant cure against cancer to everyone within their reach which includes early detection, low cost medicine, hospitals within everyone's reach?
    Anyway thanks Nobel committee to identify and promote the great works of humanity.
    #Congratulations to the luckiest scientists who worked hard and performed great work.

  10. Also in India at the same time. Yoga can cure cancer, govt may have proof in a year: Minister, AYUSH Shripad Naik

Leave a Reply

(*) Required, Your email will not be published