Annette Khaled, PhD, Professor of Medicine and Head of the Cancer Research Division at the Burnett School of Biomedical Sciences at UCF College of Medicine talks about the CellSearch system.
Interview conducted by Ivanhoe Broadcast News in July 2018.
Tell me about the cell search machine, what does it do?
Dr. Khaled: The CellSearch machine is actually about ten to twelve year old technology. It can take a small amount of a patient’s blood, basically a few tablespoons, and isolate very rare cells such as circulating tumor cells. And then you analyze the cells and determine the number and the type of circulating tumor cells that these are.
What type of tumor cells are you looking for?
Dr. Khaled: In our studies because we were funded by the Breast Cancer Research Foundation we’re focusing on breast cancer as well as lung cancer because lung cancer is a site of metastases frequently for breast cancer.
How can you tell the difference between a regular tumor cell in the blood sample versus one that has spread?
Dr. Khaled: That’s a great question. To tell the difference between a primary tumor cell and a circulating tumor cell is what we’re trying to do. There are some markers that are found on the surface of circulating tumor cells that are not present in the primary tumor but there’s really few. And so the challenge in the field is to identify what is uniquely different about these circulating tumor cells. And how can we identify them and determine how many are present in a patient. Again it’s a field that’s evolving and the technology to do the hardware basically is there, but the actual software if you think about it that way, what are the unique markers on circulating tumor cells, that’s still to be developed.
So in the sample of blood how does this machine help you in your research and what you’re looking for?
Dr. Khaled: It offers us a way to capture these rare cells. As I said, circulating tumor cells in a tube of blood could be as few as three to five cells. And we don’t really have any equipment in the lab right now that helps us to see or pull out three to five cells in a tube of millions and millions of other cells that are present. So the CellSearch technology lets us do that. It helps us capture these rare cells from a tube of blood. And then we can analyze them for whatever markers on the surface of these cells we’re interested in looking at. The most common one is EpCAM but there are other markers that we’re interested in that maybe can distinguish a different type of breast cancer or lung cancer.
Can you go in to detail about this EpCAM?
Dr. Khaled: Yes, so EpCAM is a marker that is frequently found on epithelial circulating tumor cells and it’s kind of like the main marker that most people use to identify these cells. It’s a technology around which CellSearch is based. An iron particle that is attached to an antibody to EpCAM and then using a magnet they can pull out all the cells to which this antibody to EpCAM binds and the assumption is that these are the circulating tumor cells.
Can you talk a little bit about the study that you’re working on for the women who have metastatic breast cancer in their samples?
Dr. Khaled: Sure, so to back up a little bit let me tell you it’s already pretty much been established by other scientists and other researchers that breast cancer patients who have at least five circulating tumor cells in a tube of blood probably have worse prognosis than those patients who don’t have these circulating tumor cells present in the blood. So that’s been established. We’re working on a new cancer biomarker that’s called Chaperonin-containing TCP1. And our hypothesis is that as a cancer cell changes from being a tumor cell in the primary tumor to being a freely circulating tumor cell in the blood it will actually activate and increase the activity of the chaperonin. And so what we wanted to do is compare and identify those patients who maybe have increased numbers of circulating tumor cells and find out whether their primary tumors had high levels of our chaperonin and do correlative studies to that affect. And that would help us understand the steps and changes that cancer cells undergo from the tumor to become a circulating tumor cell.
You said if they have five or more that’s a poor prognosis then?
Dr. Khaled: Yes.
Than for somebody having say one or two.
Dr. Khaled: In breast cancer the cut-off threshold was established to be at five, if you have one or two it’s not good but it’s not as bad. But usually you can have hundreds; five is kind of a low number. Many times some people have hundreds or thousands of circulating tumor cells. And that really is a very serious prognosis at that point.
And so those circulating tumor cells that means that the cancer has … ?
Dr. Khaled: Is moving basically – that the cancer may become metastatic.
What impact does having this machine for your research, what implications would that mean for future therapies, how does that help for you to do your research better?
Dr. Khaled: So what it does for us is that it opens windows to these rare cells that we didn’t have a technology to look at before. So we can design new experiments looking for these rare cells and testing these rare cells. For example, we’re developing a new therapeutic based on nanotechnology. And so we can, for example, test this using our rodent models. And then determine did we decrease the number of circulating tumor cells in these mice or not. We couldn’t do those types of experiments before because we didn’t have a way to capture these rare cells. Now with the CellSearch instruments we can do both the human correlative studies like I just mentioned or we can do new mouse studies to see what can cause circulating tumor cells and how to develop therapies that inhibit or prevent these circulating tumor cells.
Would you say that this may also be good for detection of cancer or just determining the prognosis after therapy?
Dr. Khaled: Let me distinguish two uses. The CellSearch equipment was FDA approved for clinical use but we’re not using it for clinical purposes. Our purposes are for research. And so the clinical purposes are really limited to enumeration of circulating tumor cells and correlating that with cancer prognosis. But as I said what we’re using it as a research tool . The same technology that is used clinically, we can use to capture these circulating tumor cells in our rodent model or in our specimens that we’re testing in the lab. This let’s us try out new technologies, new diagnostics, new biomarkers with this technology. But none of this is approved for patient use. It’s just as I say only for research purposes.
But for research purposes would it also be used for therapies that you are testing?
Dr. Khaled: Exactly. So this has the application and also it has potential to develop new diagnostics. As I mention the current use of the CellSearch equipment is really only limited to these EpCAM positive circulating tumor cells. That’s what’s FDA approved. We’d like to develop new methods of circulating tumor cells so it captures more of the population. It’s possible the EpCAM positive circulating tumor cells are only a small population. Maybe there’s other markers that will pick up more cells or maybe creating cocktails of markers, cocktails of antibodies that we can use. So we have a lot of ways that we can use the CellSearch to just not only optimize our therapeutic efficiencies but also diagnostic capabilities.
Can you go in to the background of how you guys acquired this machine and the reasons why?
Dr. Khaled: Everything came together beautifully in terms of us being able to acquire the CellSearch equipment. I actually had been reading for a long time about the CellSearch equipment, it was a piece of equipment that you find being cited in most high impact publications in the research field. It’s a cornerstone of a lot of research studies on circulating tumor cells. And at the same time while I was reading about the CellSearch equipment we had an opportunity with Kathy Engleman who lost her sister to colon cancer. And that was really a tragic moment for the whole family. And she (Kathy) wanted to do something to help cancer research at UCF. After meeting with her and hearing about her experiences and sharing with her what we were doing here in the lab, we just came together in a beautiful synergy. I told her about the CellSearch equipment and she right on the spot said hey, I’d love to help you guys get that. So you know here we are a few months later and thanks to Kathy and her family and their endowments we were able to purchase the equipment and now move forward with our research.
What’s the benefit?
Dr. Khaled: So one of the benefits of having the CellSearch equipment in our arsenal here at UCF is that we can do experiments where we can test therapeutics. One of the things in my lab that we’re developing is a nanotechnology based therapeutic. Up to now the only thing we could do is basically treat mice with this and just measure tumor growth or regression. But now we can do something more because we can now look for circulating tumor cells and ask whether a therapeutic actually inhibits these circulating tumor cells which basically prevents metastases. So that’s something that we couldn’t do before having the CellSearch equipment. The other thing that we also can do is we can improve the technology to isolate circulating tumor cells. So right now the only thing that’s available pretty much is EpCAM based materials that you use to isolate circulating tumor cells. But we don’t know if every single circulating tumor cell is EpCAM positive or if there are a bunch of EpCAM negative cells that were missing. We can develop new methods for isolating circulating tumor cells and test those methods with the CellSearch equipment. So this could actually impact positively in future diagnostics that people develop based on circulating tumor cells.
Do you know how common this machine is?
Dr. Khaled: It’s not very common. As far as I know we’re only two of these in Florida. One is at Moffitt and then we have the other one. I believe there used to be other ones but they’re not currently being used. As I said, this technology has been around for a while it really hasn’t advanced very much, at least the research use. But I think being bought by the new company, Menarini Silicon Biosystems, they may focus more not just the clinical side of things but also the research side of things which I think is the best potential for growth of this equipment.
You said that it’s also being used on the clinical side.
Dr. Khaled: Yes.
What are people doing on the clinical side?
Dr. Khaled: I’m not an expert in that area so take this with a grain of salt, but most of the use is basically to enumerate circulating tumors cells in a tube of blood. And to determine does this patient have five, ten, fifteen, a hundred circulating tumor cells in their blood. And then that correlates with their prognosis, their treatment, efficacy and things like that.
END OF INTERVIEW
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