[Applause] my research team and I are rare cell collectors some people collect rare stamps or Rare Coins but we've been working for over a decade to develop new systems that allow us to find and collect and profile the rarest of human cells cells that are one in a million that we think may have tremendous potential for the treatment of disease our core idea was that if we could comb through vast collections of cells from the circulation of the human body that we might be able to to find rare disease fighting cells and if we could do this type of exhaustive search for example in a cancer patient that we might be able to find incredibly rare immune cells from the blood that had encountered a tumor that knew how to recognize cancer cells and eradicate them we knew that this was going to be like looking for a needle and a hay stack but if we were successful we thought that we might be able to unlock new possibilities in the treatment or for the treatment of cancer but in order to test out this idea there was a significant technological challenge that we had to tackle a tube of blood contains 25 billion cells and as of about 5 years ago our top cell processing speed was about a million cells an hour that may sound pretty Speedy but if we want to look at all 25 billion cells in a tub of blood to find those rare tumor killing immune cells it's too slow a million cells an hour means that it's going to take us two weeks to get through that tube of blood and cells really only live outside of the Body for a couple days and so this slow processing speed was a major impediment to the search for these potentially tumor killing immune cells the reason that cell processing was so slow was because we looked at cells one at a time we would put them through instruments that would kind of put them into a single file format and serially we would an analyze them and profile them to see if they had interesting properties our big breakthrough was that we were able to massively parallelize the profiling of cells so what you're looking at here is a micro device where we're flowing through millions and millions of cells a minute and getting up to processing speeds of about a billion cells per hour so now able to get through a tube of blood in about a day once we're finished processing all of the cells even if we just have 10 or 20 in a vast background of other cells they're collected in this nice little protected pocket that is created by our x-shaped structure so this is how we were able to really move past this bottleneck of cell processing speed to really be able to look at an entire tube of blood and we've used this for a number of different applications we have looked for cells that are markers of disease in blood we have used this technology to learn new things about human biology but what I want to spend my time on today is how we've used this to look for rare immune cells and to think about how we might harness the power of those cells to create eventually a new treatment for cancer where the therapy is something that's generated from a tube of a patient's own blood treating cancer a really terrible and and often devastating disease with our own immune cells that may sound like science fiction to you but over the past decade or so the biomedical research Community has been making incredible progress in using the immune system to fight diseases like cancer our immune system uses a highly orchestrated Army of cells to patrol our bodies and keep us healthy our immune cells are always on the lookout for disease cells and if they find a cell that looks like it's taken a wrong turn they get rid of it they attack it destroy it get it out of the body and our immune system is really good at finding disease cells like cancer cells but sometimes a tumor grows too fast there are too many cancer cells the immune cells are overwhelmed sometimes cancer cells also get really tricky and they outmaneuver the immune system this is where immunotherapy comes in we can give a patient extra immune cells or give them a drug that can help boost their immune system and then this allows the immune system to do its thing and get rid of tumor cells so immunotherapy is quickly becoming a mainstream part of clinical medicine a new pillar in the treatment of cancer but there are challenges that we still have to get past immunotherapies the outcomes are sometimes mixed with patients some patients respond some patients don't we don't really know how to predict who will respond and who won't some of our immunotherapies can be quite expensive the ones that are composed of living cells sometimes cost hundreds of thousands of dollars per treatment so there's more to much more to be done in this area I want to tell you about a particular type of immunotherapy today that's called till therapy so tills are tumor infiltrating lymphocytes and till therapy is one of are most advanced cell therapies for solid tumors which are the vast majority of cancers tills are collected from tumor tissue so a part of a tumor is reected out of a cancer patient's body the cells are grown out of that tumor tissue in the lab they're multiplied expanded many copies are made of them and then they're infused back into the patient's body till therapy has been tested primarily in melanoma and we've seen really extraordinary results in the clinic subsets of patients that have been enrolled in clinical trials infused with their own immune cells have responded really dramatically to this patients with Advanced metastatic melanoma skin tumors all over their bodies all of the sudden tumor free and and tumor free for years so this is something that that really works as a therapy for cancer a patients's own immune cells but there's more to do here till therapy because you know we're growing cells out of tumor tissue there's a complex manufacturing process that needs to be carried out in order to generate these doses of cell therapy outcomes are a bit mixed in clinical trials somewhere between 20 to 30% of patients respond to this type of therapy and so there's certainly more to do and especially in thinking about how to apply this to other cancers for melanoma this is straightforward you can reect the tumor out of the skin for cancers that are more deeply buried in the body for example lung cancer it's difficult to get the tumor tissue there are some tumors that just can't be reected at all so we started thinking about a potential new new approach to maybe harness the power of something like tills but maybe make it more practical and more effective and our idea was focused on the fact that the immune cells that end up accumulating in tumor tissue they come out of the blood and we wondered whether these immune cells might sometimes leave the tumor and go back into the blood and we thought that if we could find these cells that we would have a new starting material that would allow us to to start making something like till therapy but where we started with a tube of blood so armed with our uh High throughput cell processing technology looking at a billion cells per hour we set out to look for these cells we weren't sure we would find them but we started our work in mice we looked at Mouse models of lung cancer breast cancer colon cancer melanoma searching for these immune cells in the blood and we found them we looked the signal was really weak at first we weren't even sure that what we were looking at was real but eventually we optimized we worked on our technology for collecting the cells and eventually we had enough to try them out as a therapy so we collected the cells we packaged up a mouse-sized dose of these immune cells and we injected those cells after we had multiplied them and made enough we injected them into mice carrying tumors and we saw something quite profound in many of the mice that we dosed with the cells their tumors disappeared so here you're looking at two mice one not treated with the cells the other one has been treated with the cells and you can see that tumor really having disappeared we even rechallenged these these mice with a new dose of tumor cells after they had been tumor free for months and we could see that they could still fight off the tumor cells that those immune cells that we had injected were still active in the lab we refer to these cells as as circulating tumor reactive lymphocytes you know it's a bit of a mouthful so for short we call them C LS or controls and we think this is a fitting name these are cells that seem to be able to control progression of a tumor so doing all this work in mice and finding these cells and mouse models of cancer was a great start but obviously we had to start looking in humans to see if they were present there so we looked across samples collected from patients with a variety of different tumor types using the same approach the same technology and we were able to visualize these cells in humans we tested them to see if they could react with tumor cells and kill them and they could so everything that we had learned in mice seemed to map on to what we saw in humans these cells are really rare they're about 0 one% of immune cells but we have been able to show that there's enough of them to serve as a starting material for a cell therapy so we're we're excited we're excited about this discovery we're excited about the potential of it it's also very new so the work that I've just told you about uh was really just published a few months ago so this is literally hot off the press and we do have a ways to go thank [Applause] you but what is exciting about this is its applicability we don't have to do surgery on patients we don't need tumor tissue we can use this to address many more types of solid tumors we think that there's also the potential that this approach May improve outcomes every single cell that goes into a dose of this cell therapy we selected it with our cell processing technology and so every dose has the potential to be more consistent we the instrumentation that we use to do the cell collection is not very expensive pretty small could be parked at any medical center so we're really hoping that we can keep costs down and excess accessbility high so it is early days we're very lucky we have an incredible team of people that are working away on this here in Chicago to see if we can really push this towards the clinic they are focusing in you know what tumor type should we go after what's the clinical study that needs to be run to show the efficacy of this approach and the safety we need to think about how to approach the FDA and all of these things that that one needs to consider When developing a new therapy but we're excited so I hope I've convinced you today that our Relentless search for rare cells is paying off and that we're learning something about how to use immune cells as a treatment for cancer again where that treatment starts with a tube of a patient's own blood thank you