And welcome now to The Forefront Live. Dr. Michael Bishop and Dr. Sonali Smith join us to talk about this exciting class of therapies and how this is revolutionizing the way we treat certain blood cancers. I want to remind our viewers, that we'll take your questions for our experts, but please remember that today's program is not designed to take the place of a visit with your physician. Welcome to the program.
If we could start off with having each one of you introduce yourselves, tell us a little bit about what you do here at UChicago Medicine, and then we'll launch right into the questions. And let's start with you.
Hi, I'm Michael Bishop. I am director of the cellular therapy program at the University of Chicago. I've been at the University of Chicago for now almost seven years. And my specialties are in blood cancers, and stem cell transplantation, and cell therapy.
Hi, I'm Soni Smith, and I've actually been at the University of Chicago for about 21 years. And the entire time focused on a type of blood cancer called non-Hodgkin's lymphoma. I worked very closely with Dr. Bishop since he arrived, using a lot of the new therapies that are effective for this particular disease, including immunotherapy, stem cell transplant. And part of my research also focuses on new drugs and what we call targeted small molecules.
Excellent. Well, let's just start off with the basics, and give everybody kind of a little bit of a primer, I guess you could say, on immunotherapy. And could you explain to us what that means and what that is?
Yeah. So a fantastic basic question that we all are really excited to be a part of right now. But immunotherapy is essentially using the immune system to try to fight off cancer. And there is a ton of different types of immunotherapy, whether it's designing antibodies that attack proteins that live on the surface of cells, or putting those antibodies together with a payload, almost like a Trojan horse. To something really exciting, which is like cellular therapy or CAR T therapy, which Dr. Bishop is the expert in.
So tell us a little bit about CAR T therapy and what exactly that is.
OK, so a CAR T-cell therapy, comes back to that Trojan horse analogy. So we know that our immune system has the capability of recognizing cancer, but sometimes it doesn't do a great job or we wouldn't develop cancer. So with CAR T-cell therapy, CAR stands for chimerical antigen receptor. And where that comes from is in Greek mythology, there was something called a chimera. And a chimera was a mythic creature, it had the head of the lion, the body of a goat, and the tail of a snake.
And what we do in CAR T-cell therapy is take different components. So Soni was talking about we have monoclonal antibodies. So we take a portion of the monoclonal antibody, which targets the cancer, and then we take a portion of an immune cell call a T-cell, and we use its receptor. And we put them together, that makes our chimera. The problem is, how do you get that chimera into the immune cell that you want to use for treatment.
And it comes back to the Trojan horse analogy. We actually use a virus. And that virus infects the T-cell. And you would think that would be a bad thing, but this is really a wimpy virus. It infects, but then it just happily lays inside of the cell. But it's carrying genetic material, same way like the Trojan horse carried in the soldiers. And they get released, and it gets incorporated into the cell.
And from that point on, that cell, every time it divides, will express the chimeric antigen receptor. And once it expresses that, it targets the cancer cell. And with that portion for that protein on the surface of the cell, that the cell gets activated, and then it kills the cancer cell.
It's a fascinating, fascinating technology, and fascinating treatment. We actually have a center here now that we do the work on these cells, is that correct?
That's correct. it's known as the Advanced Cellular Therapy Laboratory. This was a major multi-million dollar investment by the University of Chicago. And we will be producing our own CAR T-cells. But we also work very closely with pharmaceutical companies in order to bring new and different products here. We actually have one of the largest portfolios of clinical trials in cellular therapy in the country.
Interesting. And Dr. Smith, when we talk about clinical trials, to me, that that's always one of the special areas I think for UChicago Medicine, because we are an academic institution, we are a research institution. And I think that's important for patients, because they can come here and get some of the newest things that are being worked on. Would that be an accurate statement?
Yeah, absolutely. I think clinical trials are the way we can take science, and really make it active, and investigate it for patients where we can use it to the best of our ability to improve how well people do. Clinical trials has taken on really, an increasingly important role, certainly for the University of Chicago. This has always been a place where we've had lots of trials in different areas.
And over the last several years, there's been a shift where clinical trials used to be very what I would consider non-specific. It was somewhat random drugs being tested in diseases where we thought they might work. And today, a clinical trial is really a very targeted way of understanding the biology of a particular cancer, in this case, maybe something like lymphoma, and designing a therapy that should work based on all of the science and all of the biology we know. And by doing this, and by having targeted trials, I feel very excited to be able to discuss and offer these to patients, because I think there is a higher likelihood of this making sense in the lab, and then certainly for people.
That's fascinating. Now we did a video with you about a year ago. We did an interview with you about one of your patients, and got to follow up with him recently, and he's still doing very well. We're going to play that video here in a minute. And then we'll talk a little bit about of the treatment, and what he went through. And he has a special story because first person in Chicago that received CAR T-cell therapy. So let's go and roll that, and we'll chat about it afterwards.
Scott McIntyre is a busy guy. He works at a company he owns called Shamrock Truck Sales. You'd never guess by looking at him that he very nearly died because of cancer just two years ago.
Basically, we had a life expectancy of about six months. But in the very first part of 2016, we got a call where I was able to harvest my T-cells, and it became my turn. And so in March of 2016, I was able to receive the CAR T treatment.
Scott was one of the first people to receive CAR T-cell therapy as a trial. He was at a point in his fight with cancer where he had no other options, but CAR T gave him a chance. Michael Bishop is one of the doctors who provided care to Scott.
You pray for that every day as an oncologist that you can deliver that kind of-- you give that kind of care, and give that kind of treatment to a patient. So to say that I'm excited would be a major understatement.
In the first part of the process, T-cells, the workhorse of the immune system, are collected from the patient's blood then scientists insert instructions that enable those T-cells to find specific cancer cells. While the T-cells multiply in the lab the patient receives chemotherapy to reduce the number of cancer cells. And finally, the engineered T-cells are returned to the patient's bloodstream where they seek out and kill remaining cancer cells.
Really, what it does is program the cells to be specific for the cancer. Because we know our immune system is capable of eliminating cancer. But sometimes, it needs to be more specific and go towards the cancer itself.
Next scan, lo and behold, cancer-free. Be on remission. I've been in remission now for about 15 months. Every month gets better and better. My strength has come back, my stamina has come back. Basically, I'm back living a full life again, enjoying the things I like to enjoy. So it's just absolutely been a miracle, and I owe so much to the team at University of Chicago.
Scott and his wife, Cindy, has spent a lot of time in hospitals in recent years. They're happy to be back at work at their business and back to a normal life with a chance at a happy future ahead.
The care at University of Chicago hospital was absolutely phenomenal. I spend a lot of time on the 10th floor, of course-- up there at 10th East. And everybody was so professional, and so just compassionate with it.
That's what our purpose here is. Is we want to bring new and innovative therapies to improve the lives and particularly the quality of life for our patients.
So Scott was the first patient in Chicago for CAR T, and you both treated him. And he had such nice things to say about each one of you. So he's a nice guy. He also told me-- this video is about a year old, but I got to talk to him about a month or so ago. And he's expecting a grandchild. His life is back-- he's a huge Notre Dame fan, as we were talking beforehand. And things are going quite well for him. So congratulations on that. That's just exciting to see. And it's exciting to see that kind of exciting technology that helps people. And that's exactly what we're talking about here.
So immunotherapy and the CAR T-cell therapy and in particular, it was kind of interesting how you were describing that before we started. That basically, it's fascinating to me that you're actually modifying almost the body's immune system. And I don't know where the genesis of all of that was, but it really-- the impact is almost startling I would imagine from your standpoint. It's fantastic.
It is startling. I've said this over and over again. It's the most exciting thing I've seen in my 25 year career. I went into this with at the time, what an exciting field of bone marrow transplantation, which is actually kind of a crude adaptation, where we try to take the immune system from somebody else and put it into an individual. But the idea coming back to the genesis of this, CAR T-cells have actually been around for over 20 years.
Somebody had the idea to go, well, we know that if we take a donor's cells and do that, but could we do it with less side effects, and have not the need for a donation by a family member or by a volunteer? And it's taken research, like Soni was talking about-- in the laboratory. It took that 20 years in order to bring it to the clinic. And it's through clinical research that we have all of the treatments that we do today. I just want to emphasize that. Some people get scared about it, say, I don't want to go in research.
Well, the treatment they've received was based upon research. And if we didn't have that clinical research, We would still be back in the dark ages of oncology.
And I'm really glad you brought that up, because Dr. Smith, when I was talking with Scott, one of the things he mentioned about you is that when you were talking with was with Scott and his wife, you talked about the research, how important this was. You know, that obviously, you hoped that it would be successful with him, and it looks like it happened so far.
But his comment to me was, and I thought this was just-- it touched me, quite frankly. He said, even if it didn't work on him, he knew that at least he would be maybe helping advance the science a little bit by having this done to him. And if it didn't work out, then at least maybe it would help someone else. I thought that was really nice.
I mean, Scott and Cindy both are just very, very special people. And I think everyone who goes onto the trials, they put quite a bit of faith into the system. They put some faith in to us as their physicians, some into the trial. And our hope and our prayers are always that this is something that's going to help them and perhaps other people down the road.
And you know, when we talk about-- Mike, you mentioned that this is one of the most exciting things you've seen, I take care of people with lymphoma. And when you have somebody with a very fast growing and aggressive lymphoma, it's been a real challenge. This is still one of the hardest areas for us to overcome. And to have a trial that's based on just outstanding science and understanding of the immune system, and to be able to capitalize on it, and see somebody really come through on the other side-- this is why we do what we do.
Yeah, he's got another grandchild coming. It's an exciting time for him. I'm glad he can see it. And you mentioned before the show, which I thought we might want to talk about just for a second, 100th CAR T patient, is that correct?
That's a bunch in a short period of time.
Right. We're very excited about that. To see the 100th and the patient who is receiving the 100th, he or she was very excited about it as well. But we think that this technology can be expanded far beyond 100 patients. We know that there are patients out there who could clearly benefit from this, and our next steps are actually to take it from blood cancers and move forward to solid tumors. So in the next five years, our large focus is to make it better for patients with blood cancers, and to expand it to solid tumors.
That'll be huge potentially. That's very exciting. So let's talk about currently, who is the ideal candidate for just immunotherapies in general? What are you looking for when you look at a patient that might benefit from this?
Yeah, I think immunotherapy like we talked about at the beginning, is a pretty big term. And it includes a lot of different types of treatment. What Dr. Bishop has just talked about is the cellular therapy in CAR T, there's certainly other types of immunotherapy that have also been really exciting and very helpful to patients, including using antibodies that either break tolerance, let's say, between T-cells and the cancer cells. So just explain that for a moment.
This is a field called checkpoint inhibitors where we know that cancer cells somehow put the T-cells to sleep and the T-cells are the part of the immune system that should try to attack the cancer. And by using some of these antibodies, you can break that tolerance and allow those T-cells to really do their job.
And while this has been really active and exciting in many of the solid tumors, there's also certain types of lymphomas like Hodgkin's, where there's a really high response rate. And there are probably other types of checkpoints that we can look at. So one of the trials that we've been a part of has no offense to look at a checkpoint between a lymphoma cell and a macrophage, which is another type of immune cell.
And I really think immunotherapy is going to be something that breaks us through the next layer of trying to get rid of cancer. There's so many parts of the immune system that we can either capitalize on or activate, and somehow use to get rid of the cancer.
We want to remind our viewers that we are taking questions live on the air, so type them in the comment section. We'll try to get to as many as possible as we continue on with program. Now from the standpoint of an oncologist and a researcher, this has to be a very exciting time to be in your field, because it seems like we're on the cusp of something huge here.
I would truly say that this is one of the most exciting times in oncology. I always talk to the fellows, I go, I wish I could trade places with you because what's going to be happening in the next 10 to 15 years is it's going to be revolutionary.
And what we see, with this is just the beginning. And so we're going to see this form of therapy be joined with other forms of treatment for oncology, surgery, radiation. Even traditional chemotherapeutics will still play a role. But now, as Soni was alluding to before, it's going to be more targeted, and more specific, and more personalized. It's just not going to be one size fits all. That we'll be able to analyze a tumor, and understand its biology. And based upon that biology, we'll be able to select the specific treatments for it to hopefully optimize response, but also minimize toxicities.
And we're doing a lot of that right now from your team's standpoint. It's a team effort. And it is individualized treatment. Every patient that comes through the door, you work with that patient and their family, and you develop a care plan. And it's not just one or two doctors that are seeing that patient. It's a whole team. And I've heard that many times from patients, and they love it, because it really addresses everything that they're going through, and very important.
We emphasize that as a team approach. And the lymphoma program is an ideal example of that.
Yeah, I think it's really important-- you asked a little while ago about patient selection and who is the right person for immunotherapy. And it really isn't something that's so simple all the time. It does take a team approach. We work very closely with the cellular therapy program and the lymphoma program to decide who's an appropriate candidate. And Mike has really done an outstanding job that once somebody is selected for cellular therapy, that there is a very high bar for quality in terms of how decisions are made and how the treatment is delivered.
The only thing I just wanted to add to that, I think what really distinguishes the University of Chicago is exactly the approach. So sometimes, unfortunately, a patient will get referred for CAR T-cell therapy, and we have to say no. And that that's the hardest part. And what it is, it's this team approach that we discuss it. But then we go, what are other alternatives that are available to them? And again, having multiple experts.
So when you're coming, you're just not getting one thing. You're getting an entire team of people who are looking at you from every different perspective. And really, I think that's what distinguishes us from almost most institutions in the United States.
I think that immunotherapy, as exciting as it is, it's not yet ready for prime time and everybody. And really trying to figure out one, who is the right patient, what are the other options, and how do we comprehensively take care of them is something I think we do very well. It's a very close knit community within our section.
Can we talk a little bit about stem cell transplantation, what that is, and how that differs?
So stem cell trans plantation, you think of the stem cell as the seed of the bone marrow. And in the stem cells actually give rise to all of the blood components, including the immune system. So stem cell transplantation has been around almost 40 years now. So it's hard for me to imagine-- actually, approaching 50 years.
And there's two forms of stem cell transplantation. There is one where the patient uses their own stem cells and this is often applied to lymphomas. And then there is another form called allogeneic, where you get it from a donor. So you always hear about doing a donor search. And that can be from a brother or a sister or from a volunteer donor. In autologous stem cell transplantation, the main purpose is so that we can give high doses of chemotherapy to overcome resistant malignant cells.
In an allogeneic transplant, we're actually trying to give this new immune system similar to CAR T-cells. But with that new immune system, there can be a lot of complications. And it takes a large team to manage those complications. But it can be highly successful and in many cases, curative. And so in that situation, the benefits outweigh those large risk.
And in the first example you gave where the patient is their own donor, they get their own stem cells back after they have had their there are other therapies and treatments to aid them in recovery, correct?
That's correct. And that's what it really does, is aids them in recovery. Because when we give those high doses of chemotherapy, it wipes out their bone marrow, and it's hard for their blood counts to recover. But by storing away the seeds, we kind of replant the garden.
Yeah. so you talked a little bit about moving in particular the CAR T therapy from the blood cancers to the solid tumor cancers. What's happening there? You mentioned five years, we're thinking, possibly? Not that I'm going to hold you to it.
No, I hope not. I wish it could be faster. Solid tumors present a far bigger challenge for us than blood cancers for a variety of reasons. We don't have the targets that we do in blood cancers that would make it relatively safe. And then solid tumors, just by their physical being, trying to get a CAR T-cell or a T-cell in there is like going through a briar patch. And in fact, the analogy that's often been used as a more hostile environment.
So there's going to be those barriers. However, there are people working on this at our own institution. And in fact, a number of people at the University of Chicago are trying to overcome these barriers. And so that's why I am optimistic that in five years, we'll start to see some of the clinical results that will benefit patients.
That's exciting as well. So Dr. Smith, from your standpoint, what do you see on the horizon that is most exciting to you as far as research and things that we can look forward to?
I think the most important part, as Mike said, these are really exciting times. Immunotherapy has evolved to allow us to be very personalized with the therapies that we have. But I think what the next few years are really going to show us is how to optimize this. How do you make it available to more people. How do you make it safer. How do you figure out which person is more likely to respond.
And we have several people here who are studying this very actively, both directly by looking at models, or in patient specimens. And we have a lot of data that's being collected. And I do think that this is going to allow us to expand the therapy even further.
I think the other piece of it, particularly when it comes to safety, as Mike was saying, I mean, this is something where you need a specialized team not only to manage when you give the cellular therapy, but also afterwards. And I think trying to make it safer by working together is the way we're going to be heading.
It's interesting, and I think we were actually talking during the video, so nobody else got to hear this, but we were talking a little bit about the facility. And I know we mentioned it also on the program, the facility that is new here for the CAR T-cell therapy. And even at the outset of this therapy when Scott had his treatment, I think at first, didn't you have to ship the cells off to have the treatment done, and then wait for them to come back?
So even that is a little bit more accessible at this point as it gains popularity.
And remember, when Scott was participating in the trial, we actually had to wait and take turns, because there was a limited capacity to make these cells. So there were patients all around the world who were all in line, waiting. And only if at that particular time, if their disease was just right they were just right, were they able to receive this therapy. So now there's greater capacity across the country. And yet we still look at that as a limiting factor in people receiving these therapies. And so have the ability to make the cells here on site will increase that capacity.
But we're also, which is even more exciting, we have what are called off the shelf CAR T-cells. And these have been again, genetically modified. So that it was taking a young person, maybe 20 years old, and they went through as a collection of their T-cells. And that was enough to generate 400 products. And then these cells are modified so that they could be given to anyone at any time.
So if you have somebody with a really, really aggressive lymphoma, like Soni was talking about before, and you can't wait, because generally it takes two to three weeks to generate these CAR T-cells in the laboratory, what if you could just call your pharmacist and go, hey, I have a lymphoma patient, and we need to treat them tomorrow? They could say, OK, here they are, write the prescription. And all of a sudden, they're delivering it to the bedside.
And we have three trials here at the University of Chicago, first in human trials of these off the shelf allogenenc CAR T-cells. I had no idea. See, you heard it here first. We're a news source now. That's very exciting.
That is very exciting.
Really, really great. So that kind of leads me to my final question for you. What are you most excited about just in cancer treatment that you see coming?
Oh, I am very bullish on immunotherapy. I really do. I hate to use the analogy-- I love automobiles-- but these CAR T-cells we're in the Model T phase right now. We want to get to everybody use Tesla-- I want to say we want to get to the Bugatti phase of this therapy. And we're seeing this on a daily basis. I really do think that these will in five years look archaic. That we'll have so much more potent CAR T-cells. We'll have these off the shelf. We'll be able to control disease. We'll be able to control toxicities. And we'll have active I mean, accessibility immediately. So I think the next 5 to 10 years are going to be extremely exciting.
What a wonderful time to be involved in this. You all are doing fantastic work. And it's great to see, and it's exciting to see it all unfold before us. Thanks for being on the program.
Oh, thank you.
Thank you for having us.
You both did a wonderful job. That's all the time we have. Please remember to check out our Facebook page for future programs and other healthy living tips. Also, if you want more information about UChicago Medicine, please take a look at our website at UChicago.org.
If you need an appointment, you can give us a call at 888-824-0200. Thanks again for watching. Hope you have a great week.
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Frequently Asked Questions About CAR T-cell Therapy
Currently, CAR T-cell therapy is available for patients with acute lymphoblastic (lymphocytic) leukemia (children and young adults) and certain types of non-Hodgkin lymphoma (adults) who do not respond to standard therapy or who have relapsed after at least two other kinds of treatment failed. We are conducting clinical trials of CAR T-cell therapy for several other cancers, including multiple myeloma, cervical cancer and non-small cell lung cancer, and continue to investigate other conditions that may benefit from CAR T-cell therapy.
Our physicians have the experience and expertise to evaluate each patient to determine if CAR T-cell therapy has a high chance for success.
The FDA recently approved CAR T-cell therapy for the following conditions:
- Acute lymphoblastic leukemia (for young adults age 25 and younger)
- Certain types of non-Hodgkin lymphoma including:
- Diffuse large B-cell lymphoma (DLBCL)
- Primary mediastinal large B-cell lymphoma
- High grade B-cell lymphoma
- Transformed follicular lymphoma
- Acute lymphoblastic leukemia
Clinical trials of CAR T-cell therapy are being offered at the University of Chicago Medicine for the following conditions:
- Acute lymphoblastic (lymphocytic) leukemia (for ages 18 and older)
- Cervical cancer
- Follicular lymphoma
- Head and neck cancer
- Mantle cell lymphoma
- Multiple myeloma
- Non-small cell lung cancer
Approximately 40 to 60 percent of patients who undergo CAR T-cell therapy experience side effects. Some of these symptoms can be managed with intravenous fluids and acetaminophen. But CAR T-cell therapy often triggers serious conditions, usually within five days of infusion. These may include:
- Flu-like symptoms, such as fever, fatigue, shortness of breath and chills
- Racing heart beat
- Drop in blood pressure
- Neurologic conditions, such as headaches and seizures
- Short-term memory and cognitive issues
These symptoms are reversible but may require a stay in an intensive care unit. Researchers are actively studying better ways to reduce the side effects of CAR T-cell therapy.
Patients who undergo CAR T-cell therapy typically do not lose their hair or experience some of the other common side effects of chemotherapy, such as nausea and vomiting.
Once the patient completes the treatment and returns home, risk of cancer recurrence is considered low. Patients can be monitored by their primary physician while staying in communication with the UChicago Medicine CAR T-cell therapy team.
If CAR T-cell therapy is not an option, there may be other treatments available. As recognized leaders in research and clinical trials of emerging therapies for cancer, we are able to bring the latest treatments to our patients sooner. Advances in genetic testing and imaging, as well as innovative combinations of immunotherapy, chemotherapy, radiation, stem cell transplant and surgery, are offering patients more diagnostic tools and treatments — and more hope for a cure — than ever before.
CAR T-cell therapy has the potential to change the course of treatment for many types of cancer. Results from CAR T-cell therapy have been impressive, but the treatment is still relatively new and requires more research. Studying patients who participated in CAR T-cell clinical trials over time will provide more information about the treatment and its long-term effectiveness.
Researchers and physicians at UChicago Medicine, in the U.S. and around the world, believe that CAR T-cell therapy will serve as a foundation for even more and better cancer treatments. We are actively investigating the expansion of CAR T-cell therapy to treat other types of blood cancers as well as solid tumor cancers.
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We are a National Cancer Institute (NCI) Comprehensive Cancer Center — one of only two in Illinois. As a leading center for phase 1 and other early-phase clinical trials, our physician-scientists are creating new treatment protocols that later become the standard of care elsewhere.
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Our physicians work to bring the latest breakthroughs in cellular therapy treatments quickly to their patients’ bedsides. Several new cellular therapies are now being tested through clinical trials for blood cancers and solid tumors.
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