Here is the full transcript of Dr. Shana Kelley’s talk titled “Is The Cure For Cancer Already Inside Us?” at TEDxChicago conference.
Scientist Dr. Shana Kelley’s talk, “Is The Cure For Cancer Already Inside Us?”, explores the groundbreaking research conducted by her team in the field of rare cell collection and profiling, with a focus on finding rare immune cells capable of fighting cancer. She describes the technological challenges they faced, such as the slow processing speed of cell analysis, and their breakthrough in massively parallelizing cell profiling, which significantly accelerated their research.
Kelley discusses the potential of using the body’s own immune cells for cancer treatment, highlighting the advances in immunotherapy, especially TIL therapy for solid tumors, and its remarkable success in treating melanoma. However, she notes the limitations and high costs associated with current immunotherapies.
The talk shifts to introduce their novel approach of using circulating tumor-reactive lymphocytes (CTRLs) found in blood, bypassing the need for tumor tissue and potentially offering a more practical and effective treatment. This method has shown promising results in mice, leading to the disappearance of tumors and sustained immune response. Kelley expresses optimism about the future of this research, emphasizing its potential to transform cancer treatment by harnessing the power of the immune system, making it more accessible and cost-effective.
Listen to the audio version here:
TRANSCRIPT:
Introduction to Rare Cell Research
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, 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, we might be able to find rare disease-fighting cells. And if we could do this type of exhaustive search, for example, in a cancer patient, we might be able to find incredibly rare immune cells from the blood that had encountered a tumor, knew how to recognize cancer cells, and eradicate them. We knew that this was going to be like looking for a needle in a haystack. 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.
Technological Challenges and Breakthroughs
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 five 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 tube 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 of 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 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.
Applications in Cancer Treatment
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 often devastating disease with our own immune cells, 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 much more to be done in this area.
Innovations in Immunotherapy
I want to tell you about a particular type of immunotherapy today that’s called TIL therapy. So TILs are tumor infiltrating lymphocytes. And TIL therapy is one of our most advanced cell therapies for solid tumors, which are the vast majority of cancers. TILs are collected from tumor tissue. So part of a tumor is resected 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.
TIL 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 tumor-free for years. So this is something that really works as a therapy for cancer, a patient’s own immune cells.
But there’s more to do here. TIL therapy, because 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 resect 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 resected at all. So we started thinking about a potential new approach to maybe harness the power of something like TILs, 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 start making something like TIL therapy, but where we started with a tube of blood.
So armed with our 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. 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.
From Laboratory to Clinic
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 re-challenged 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 circulating tumor-reactive lymphocytes. It’s a bit of a mouthful. So for short, we call them CTRLs, 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 in 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 0.01% 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 excited. We’re excited about this discovery.
The Future of Cell Therapy
We’re excited about the potential of it. It’s also very new. So the work that I’ve just told you about 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 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 is 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. 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 accessibility 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 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.