Feb 12, 2020

Interview Transcript

Interviewer: Headlines are talking about a discovery that could lead to a one-size-fits-all cancer treatment. Is it realistic or is it hype? We'll talk about that next on The Scope.

I'm talking with Dr. John Phillips, professor of hematology at University of Utah Health. Dr. Phillips, first of all, what was your involvement with this research discovery?

Dr. Philips: We have been involved with a group at Cardiff. I met the senior author, Professor Andy Sewell when he was a postdoc here at the University of Utah 25 years ago. And our collaborative relationship has extended the last 25 years, and we work together at solving complex biological problems. And we collaborate on a number of things, but in this case, Professor Sewell came to me specifically asking how to screen for molecules that were required for cancer recognition by these T-cells.

Interviewer: So since this paper has come out, what's been the response?

Dr. Philips: It's been sort of overwhelming in some regards. First of all, I have multiple emails every day since the last a week and a half from people around the globe really who are either scientists wanting to know exactly what methods we used in our screening process to individual people who have identified my email address and are sending me questions like I have a family member, a friend who has some type of cancer that they want to be treated with this therapy.

Interviewer: So I mean, a lot of excitement, a lot of interest. What is everybody excited about? What did this paper show?

Dr. Philips: Well, the T-cell that we are describing in this manuscript is a T-cell that can recognize an antigen presented on some types of cancer in the context of a molecule called MR1. And the interesting thing about this is all humans have nearly identical MR1, this is why people are saying that it's sort of a universal anti-cancer therapy.

Interviewer: The excitement is that this could lead to an immune cell therapy that could treat many types of cancer in many people, is that the idea?

Dr. Philips: So, yeah, the idea is so I think, there has been a lot of excitement recently in the sort of the last four or five years about engineered T-cells called CAR T-cells that are specifically manufactured from a patient to recognize a very specific molecule on a tumor type. And those cells are grown in culture, in a laboratory from the patient and then given back to the patient where they attack a very specific type of cancer. These have been very, very beneficial for people. And this is just another type of T-cell can potentially do the same thing but without that engineering aspect needed to be applied to it.

Interviewer: So what are the limitations of the CAR T-cell therapy that this work with this cell might overcome?

Dr. Philips: Well, right now, the, the majority of CAR-T therapies are directed towards hematologic malignancies, so leukemias and lymphomas of specifically of the B-cell origin. There are things certainly in the laboratory and that commercial entities are working on to sort of expand those CAR-Ts to more solid tumor types but right now it really is hematologic tumors. What the molecule that we're looking at is directed towards is it certainly will work on hematologic tumors, but it will also work on solid tumors which expands the scope really of the types of cancer that can be treated.

Interviewer: And so how did you go about, or how did this research team go about figuring that out? What was the work that, you know, kind of showed what this T-cell could do?

Dr. Philips: Well, the T-cell was actually identified several years ago and the team in Cardiff identified it as a cell that could kill cancer cells. They expanded the panel of types of cancer cells that they could assay in the laboratory and they found, you know, what types of cancers it would and would not kill.

And then they were interested in what molecule is being seen, where like, why does this T-cell want to kill this cancer cell? And that's sort of where I became involved using as in the title it says CRISPR-Cas9 screening method. So we used a CRISPR method which goes in and modifies DNA. So we went in and knocked out every single in the genome and then screened for cells that were able to escape being killed by this killer T-cell.

And once we had identified those cells, we can then look at what molecules on the surface are being recognized and that sort of that work was all done in collaboration with this team at Cardiff.

Interviewer: And so, you know, there are a lot of exciting implications, but we're actually a long way from getting to an actual treatment that can be applied to patients. Can you talk about that a little bit? If you had to talk to some of these patients who are emailing you and who are hopeful that this will lead to something, what would you tell them?

Dr. Philips: Well, so we've done a lot of work in the laboratory where we sort of have characterized the molecule and the interactions with the T-cell, we've even translated that to a mouse model but that's really about as far as we've gone. What we now need to do now is we need to figure out how to translate that preliminary animal work into like a phase one study in humans.

We have not done that, you know, working with academic partners and commercial entities. We hope to sort of move that forward in the near future but during this conversation that really has not occurred yet. And so this will take quite a bit of time, I won't give you a number of days, weeks, or years that it's going to take, but this will take a significant amount of time in order to sort of move forward to actually go from a laboratory observation to a clinical trial and then sort of a commercial cure for certain types of cancer.

Interviewer: And so if this treatment were to come to fruition, what would that look like do you think?

Dr. Philips: Well, so I think in this case, what it would be is there would be a manufacturing facility that would expand this type of T-cell. And we would do clinical trials to say, if we gave you, you know, 10 to the 10th of these T-cells, they would be sufficient to kill a tumor burden of, you know, a certain size or mass. And I think it would take, you know, several trials to figure out, you know, what's the optimal dosing, what's, you know, do we want to give multiple rounds of these cells? So I think, you know, again, because this is really a laboratory observation and hasn't made it to the even in the phase one clinical trial stage, we need to be a little bit cautious in what we say as far as what this is going to look like as an eventual therapy.

Interviewer: Sure. Nevertheless, are you excited by what's come out so far in the research?

Dr. Philips: Absolutely. I think this has been very exciting. I mean, I think, you know, I have published quite a few papers in my scientific career. I don't think any publication that I've been a part of has had global response that this has had. You know, I'm getting email from truly from people across the globe, when I look at the metrics associated with this manuscript in "Nature Immunology," this has gone, I guess mainstream very, very quickly. And, as of you know, as of this morning, there were 128 articles that were sort of written in other media outlets regarding this. This certainly is the biggest impact paper that I've been a part of.

Interviewer: Well, very good and congratulations. Is there anything else you'd like to say?

Dr. Philips: Well, I think this once again illustrates that science today is very collaborative. It's these big discoveries, you know, they're really team-based discoveries. And, you know, I was just a small part of this as were people in my laboratory and that without sort of this collaborative effort, it's difficult to make these discoveries.

Interviewer: Very good. Thank you very much.

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