Annette Khaled, PhD, Professor and Head of the Cancer Research Division at the Burnett School of Biomedical Sciences at the University of Central Florida, talks about some of the research being done with focus on a protein forming complex that could be used towards therapy treatment options for cancer and how she developed the nickname cancer assassin.
Interview conducted by Ivanhoe Broadcast News in November 2017.
Can you tell me about your research, what it is and what you’re looking at and what you found through it?
Khaled: I’m a basic scientist. So what I do is understand how things work, either under normal situations like our normal body conditions or when things go wrong, for example during cancer. And then we make the basic science discoveries of how things work. A lot of times from that type of research, we can actually spinoff new ideas for therapies. So that’s what my lab has done, we were studying a protein that’s usually involved in killing cells and by studying that protein, how it works, we actually found a way of turning it into a therapy. And that’s what we’re working on right now we’re developing that therapy, were validating it, and we’re testing it to see does it kill every single cancer cell under the planet or does it kill only certain cancer cells? How does it affect normal cells, could it cause side effects in the future when we use it in patients? These are the type of studies that were doing right now with that therapy that we found.
What was the protein that you were studying, what were the results of it? Did it kill healthy cells, or did it only kill bad cells?
Khaled: What’s really interesting is that it killed some cells, but not all cells. Actually it took us a while to figure out why that was happening. It’s actually not even a protein, it’s a small little piece of a protein we call peptide. It’s 20 amino acids in length, and when introduced into the cells, some cells live and some cells die. So by sorting that part out, we learned that it’s actually inhibiting another large protein complex that folds other proteins. What this large protein complex normally does is that it takes new proteins, when they’re first made and are linear, like spaghetti in a string, and it folds them into the proper three-dimensional structure so that they function properly. This protein complex in cancer cells is highly expressed and that was one of our major findings. While normal cells need it, they don’t need so much of it. As a result we have what’s called a therapeutic window. We can inhibit maybe 40 or 50 percent of the activity is that this protein folding complex with our therapy in cancer cells and kill the cancer cells. But inhibiting the same amount in normal cells, they are fine, they’re not affected. So that’s what we learned from why we were killing some cells and not killing other cells with our therapy.
You mentioned highly expressed can you go on the details about that, when you found the protein?
Khaled: Sure. Cancer patients when they are diagnosed, they get biopsies. We can look at those biopsies, from cancer patients, of the tumors, and actually quantitate how much of our protein of interest is in that tumor. By doing those types of things we were able to find that a large number of patients, I would say over 50 percent of breast cancer patients, if not more, had very high levels of the protein that our therapy is targeting. And when we looked at prostate cancer we found very similar trends. We just published a paper about lung cancer also finding very similar trends.
And of the protein that the peptide came from?
Khaled: Our peptide is called CT20p and it actually stands for C terminus, which is the end of the protein, 20 amino acids or CT20 and by serendipity’s the target is called chaperonin-containing TCP1. So another CCT in our story. But it is really interesting that this little peptide that’s very, very small can actually affect this very, very large, complex that full of proteins.
Explain what a SEVA-108 was?
Khaled: SEVA is actually the name of the company that licensed our peptide. And they just arbitrarily gave it a number 108. So while I called CT20 peptide in the laboratory actually clinically is going to be called SEVA-108.
So it just the same thing.
Khaled: It’s the same thing.
Okay. What kind of treatment in this leading to?
Khaled: So we’re trying to target those cancers that had metastasized. Those cancers that had left the primary tumor location and now moved throughout the body and are actually the main cause of death in cancer. People don’t always die from the primary cancer, if it’s in the breast or the prostrate. They die when that cancer moved to another tissue, like the lungs or the brain or your bones. So we are trying to find a treatment for those types of cancers. The way it works is that a cancer cell, when it is ready to move, really changes its whole dynamic. The cancer becomes a very different beast when it leaves the tumor and starts to move throughout the body. And those changes are actually controlled by a number of proteins that our target, that large protein forming complex, actually processes. So what we’re trying to develop is a therapy that can hit the cancer cell at a very critical point in their biology and remove the things that they need to survive. So we can kill the cancer cells and prevent them from spreading throughout the body and affecting these other organs.
What implications can this have were somebody is going through breast cancer that has metastasized?
Khaled: Right now the survival rates are really low. And even most of the therapies, they improve survival for just a few months. I’m really hoping what we have in our hands is something that will not only improve survival for more than just a few months but rather years, and may actually lead to a cure. Because the way I envision this therapy working, is it’s going to actually work alongside what we call our immune system. These are the cells that normally protect us from infection. What we are hoping is that we can use this therapy to kill the cancer cells. And in turn those cancer cells will turn into little cancer vaccines, where they can go around and activate the immune cells, and actually teach the immune system to target these cancer cells in the future. Very optimistic and very ambitious, but I hope that that’s the way our therapy will wind up being used.
Could you just explain again what stage in the process are you in?
Khaled: We are in the stage called preclinical. What we’re doing right now is testing. We’re validating and we’re finding what type of cells are being killed with this therapy. How does it affect normal cells, are normal cells more resistant, and how does this happen? So we can actually understand how our therapies are going to work when it actually moves into a human being.
And how far away are you from clinical trials and possibly putting this into use?
Khaled: We are in preclinical right now; there is a series of steps that we have to go through. We have to first get what’s called an investigational new drug application to the FDA. Once that happens then we move into Phase I and II/III clinical trials. So I would say we’re probably at least a couple years away from getting that FDA approval and moving into Phase I clinical trials.
I read you are called the cancer assassin, can you talk about that little bit?
Khaled: This is a few years back, when we had first discovered what our peptide was doing, but we didn’t have the full story yet, we didn’t know the target. We did know the protein-folding complex, but we were just learning about it. There is an organization called the Florida Breast Cancer Foundation and they liked the idea of what I was doing. So they gave us some funding to start these initial studies. At that point one of our marketing folks decided you know they would do a story on this, the funding I had just gotten, and they coined the name cancer assassin. So that’s how the name came up. It was just noting that I received this funding and they thought it was really cool idea.
The delivery system, do use nanotechnology?
Khaled: Yes, we use nanotechnology.
Can you explain what that is?
Khaled: Our therapy really is based on this small 20 amino acid peptide. But if we were to introduce that, just as it is, into the body, it would be destroyed almost immediately because there are enzymes (proteases and peptidases) in our blood that would just destroy this peptide. So to protect the peptide, while it’s traveling through the blood to get to the tumor, we’re using a vehicle commonly called a nanoparticle. This nanoparticle is based on a polyester, like a polyester polymer, and we are able to basically encapsulate our peptide within this very small little polyester polymer that forms very, very small spherical nanoparticles that actually keep the peptide inside, so it’s protected from the environment, in the blood or in the tissues. And we can address that nanoparticle and say – take it to this tumor. So that nanoparticle will actually reach the tumors and be taken up by the tumor cells and then inside the tumor cells our peptide is released.
So it would not affect like healthy cells.
Khaled: Healthy cells should not take it up, if we did the addressing part right, if we do that address correctly the normal cells should not take up the nanoparticles.
Have you got anything else you like to add?
Khaled: Well in our laboratory here, we’re working on a cancer therapy. We’re working on new discoveries, the next generation of cancer treatments. We also train, we’re actually a training lab and I have students, both from undergraduate through doctoral studies to medical school. They’re doing this work. And so they’re learning at the very early stages how to make this discovery happen and that they’re doing in the lab could benefit patients in the future.
What goes through your head when you know that people hear the cancer assassin and think of you? Do you mind a nickname?
Khaled: Actually I think it is great because it gives hope. I receive lots of emails from different people who are telling me you know we love what you’re doing now, we want to pray for you, help you, do whatever we can just to make sure that what you’re doing can move forward. So for me it’s a hope that I think people can see that we’re just not sitting on our backs and doing nonething, we’re actually working really, really hard in the lab to find a cure for cancer.
I understand that you may have a personal connection with breast cancer?
Khaled: It was actually not breast cancer, but my grandmother had endometrial cancer. I was probably twelve or thirteen at the time. It just impressed me how this very vigorous, vital woman during this period of time sjust changed so dramatically. Her health went bad, she developed anemia, so many things happened to her and she was really never the same. She lived twenty or thirty years after that, she didn’t die from the cancer, but just the change in her body and the effects that she had from the treatments really stayed with me.
Compared to the treatment that we have right now available, how can this better improve or enhance those treatments?
Khaled: A lot of the treatments that are currently being used by doctors are effective on cells that are growing very rapidly. But cancer cells don’t always grow rapidly, especially those that metastasized. They basically move around the body, they hide; they evade the normal systems that our body has to destroy them. So these drugs that are targeting just growing and proliferating cells are not very effective when a tumor cell is not dividing, or its hiding or just moving around the body. That’s where I think these new technologies, these new therapies that we’re all developing are going. We’re trying to address that component that is missing. How can we develop therapies that are not just going to get rid of the cells that are dividing but these cells when they become migratory, when they become senescent, when they hide in the body, how can we get those cells as well?
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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Christin Senior
Annette Khaled
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