Alicia Morgans: Hi, I'm so excited to be here with Dr. Sophia Kamran of the Massachusetts General Hospital in Boston. Thank you so much for talking with me.

Sophia Kamran: Absolutely. I'm happy to be here.

Alicia Morgans: Well, wonderful. I'm happy to have you and really excited to talk with you about your Young Investigator Award from 2021. Can you tell everyone a little bit about what you proposed?

Sophia Kamran: Sure. So I'm a radiation oncologist and so thus I'm very interested in how we can harness radiation to improve patient outcomes for our prostate cancer patients. In particular, there's a very exciting space in the oligometastatic disease space for oligometastatic prostate cancer. Basically, this is an area where there's been previous data demonstrating that radiation can be used to improve outcomes, potentially halt the progression of oligometastatic disease to more advanced metastatic disease.

However, it's not fully understood and in addition, there's been a lot of novel molecular imaging that we probably all know about PSMA-PET, things like that, that is muddying the picture where we're not really sure how to define oligometastatic disease anymore. How it used to be defined isn't how really what we're seeing nowadays and so the definition is all over the place.

So I'm trying to understand how we can establish a more biological definition of oligometastatic prostate cancer. And in addition, again, with the prior studies demonstrating that there maybe a role for radiation to halt the progression, it's not well understood. Sometimes there is this halt of progression that is demonstrated and sometimes we don't understand and we don't see it in terms of radiation doses, what we need to treat to really see this benefit all over the place. Not very well understood.

So I'm also trying to understand or study the interaction of radiation with the immune system because we do think that there's an immune component that promotes the benefit with the radiation therapy in oligometastatic prostate cancer, but no one really has fully understood it or it's not very well studied, and so that's what I'm trying to look at. So it's really just establishing a more biological definition of oligometastatic prostate cancer, and then also understanding the radiation immune effect, modular effect, that can promote benefit in oligometastatic disease space.

Alicia Morgans: Well, wow, that really is so much to do in a short three year time span. I would assume there are some either biopsies or blood-based assays that you're doing to really understand the immune modulation or immune effects. And are you also using those in your biologic definition of oligometastatic disease? It sounds like you're not just relying on radiographic evidence.

Sophia Kamran: Yes. Exactly. Yes. So we're going from a biology based approach. So basically we're collecting tissue from these patients, we're also collecting blood. So we're doing longitudinal sampling, which I think is very exciting. So I've been collecting for over the past few years actually, I've kind of amassed a biospecimen repository of these samples prior to radiation, immediately after radiation, three months after radiation, and then six months after radiation.

And then I'm hoping to study using these different assays, we're going to be using TCR sequencing, CyTOF analyses, and then of course the actual tissue based analyses to kind of put the whole story together and understand what's going on in the immune system. And then also comparing oligometastatic patients, in terms of their tissue, their blood-based assays, and comparing two widely metastatic prostate cancer patients to see what the differences are.

Alicia Morgans: Wonderful. Well, tell me, it sounds like you've accomplished at least a fair amount of work, you've got this data repository that's already been ongoing. Anything else you've done in the last year since this award was awarded?

Sophia Kamran: Yeah, so we've done a little bit looking at some of the TCR sequencing in the longitudinal assays and what we have found is that in patients that have high clonal productivity immediately after radiation, that has appeared to associate with improved long-term response to the radiation therapy. So that's one thing that we're going to explore for further. That was just done in a few patients.

And then in the past six months or so, I've been really trying to optimize the CyTOF analysis. So CyTOF is this really exciting assay where we can really kind of look at the immune profiling, but it takes a little time to tinker with it and get it right, especially with the staining of the markers and everything like that.

So we've been doing it in actually just running the mill high risk prostate cancer patients who just receive radiation therapy. And we're actually seeing some really exciting changes immediately after radiation and at the three month space in terms of expression of markers, increased expression in terms of T-cells. So I think that we're going to see, now that we've optimized that assay, we're going to put it into the oligometastatic disease space and I think we're going to see some exciting results.

Alicia Morgans: Wonderful. So what are some of the milestones you expect to hit in the next couple of years until the award essentially completes?

Sophia Kamran: Yeah, so I think that I'm really hoping to, again, profile the oligometastatic patients that we do have collected using TCR sequencing, the CyTOF, and then some of the tissue based assays that I plan to do and hopefully publish a paper. And then use this preliminary data because again, it's a smaller set, but then also use it to apply for a larger grant to help me continue to fund my lab and fund for other studies.

And then eventually if we can really harness a time point where we think that the immune system is well primed, I mean maybe we can design a trial to see if we can introduce some type of an additional immunostimulatory drug, potentially maybe immunotherapy or something like that. We don't know what the future's going to hold. There's a lot of exciting developments in this area, but that would be what we ideally do in the future.

Alicia Morgans: Well, it's extremely exciting and I am sure that if anyone can get all of these tests accomplished, it is you, Dr. Kamran. So thank you so much for talking this through. Congratulations on your award, and we look forward to hearing more.

Sophia Kamran: Thank you.