Engineered Cell Therapies for Metastatic Castrate-Resistant Prostate Cancer - Saul Priceman

January 10, 2023

At the 29th Annual Prostate Cancer Foundation (PCF) Scientific Retreat Dr Saul Priceman joins Alicia Morgans in a discussion on clinic-ready CAR T cell therapies for Metastatic castrate-resistant prostate cancer (mCRPC) that can overcome the limitations of prior CAR T cell products for prostate cancer. Dr. Priceman highlights the role of PCF's funds in impacting these research efforts. The project of developing engineered cell therapies for mCRPC to increase efficacy and decrease toxicity may ultimately lead to a powerful new arsenal of immunotherapy treatments for advanced prostate cancer patients that are effective in racially diverse populations and against heterogeneous advanced disease types. This knowledge may also advance immunotherapy in patients with other types of solid tumors.

Biographies:

Saul Priceman, PhD, Assistant Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Durante, CA

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


Read the Full Video Transcript

Alicia Morgans: Hi. I'm so excited to be here with Dr. Saul Priceman, who is of City of Hope, and is going to talk to us about his most recent, one of many, Prostate Cancer Foundation Challenge and other awards. So, thank you so much for being here.

Saul Priceman: Pleasure.

Alicia Morgans: I'd love to hear about your most recent award. But you can warm us up to that award with the brief history of what the Prostate Cancer Foundation has funded in your lab before.

Saul Priceman: Yeah. So, the most recent award is funding the clinical trial with an adoptive T-cell therapy, which is an immunotherapy, a cell-based immunotherapy, for patients with metastatic castration resistant prostate cancer. And we started that trial about three years ago, and we're seeing pretty interesting responses. We're now finishing that trial and initiating accommodation trial at City of Hope in the same patient population. But we're excited to embark on that. It should be at the beginning of next year. And the research really initiated about seven years ago with Prostate Cancer Foundation who charged us with developing a cell-based immunotherapy for patients with prostate cancer. I think we were one of two institutions in the nation interested in that. And we embarked on that, again, about seven years ago from concept to getting into the laboratory and developing that therapy to what's called an IND package that we submit to the FDA to get approval to treat humans. And starting that trial, again, several years ago.

Alicia Morgans: So, one thing I noticed that you said, and I really want to pick up on it, is that there's been a lot of interest in cell based therapies, but the interest in applying them in prostate cancer has been less enthusiastic. So, what was it, specifically, that drew you to prostate cancer to apply these really novel, but sometimes somewhat difficult to endure, treatments?

Saul Priceman: Yeah.

Alicia Morgans: What do you think?

Saul Priceman: Yeah, I think there are three major themes that got us interested in prostate cancer and our specific cell therapy, which is called chimeric antigen receptor-based T-cell therapy. But it's an engineered immune cell therapy. And one of them was Sipuleucel-T, which was approved for patients with metastatic prostate cancer. And while the therapy results and survival weren't hugely beneficial to patients, it clearly was an insight that immunotherapy could work and adoptive transfer of cells could work in those patients, which was exciting to that. That was actually the first FDA approved cell therapy, and it happened to be in prostate cancer. And with CAR T-cell therapies, we had exceptional responses in hematologic malignancies, like leukemia and lymphoma. And I think we were a little naive 10 or so years ago when we were seeing these durable and curative responses in patients with liquid cancers and saying, "Well, we can apply that to prostate cancer, and we'll get the same results." And of course, that hasn't held up. But we are committed to developing effective cell therapies and immunotherapies for patients with prostate cancer, and we continue to strive for that goal.

Alicia Morgans: Well, what are some of the lessons learned from the funding that you've had from the work that is ongoing? And of course, where are you going in the future? Because I know that this is something that continues to really show quite a bit of promise.

Saul Priceman: Yeah. We, in the field, have seen several clear hints that CAR T-cells and other immunotherapies may work in prostate cancer. We've had some pretty outstanding responses in patients on our clinical trial, but there's clearly a window where we need to improve to get effective therapies. But the responses that, again, we see in hematologic malignancies. I think the lessons learned is that the solid tumor space and prostate cancer is no exception to that, is difficult to treat, especially in the advanced stages, and particularly with immunotherapy. Prostate cancers are what we call immunologically cold. They don't have a lot of immune response happening in the tumor. And so, we've learned that we have to instigate that immune response and empower the tumors and the immune system to be able to see prostate cancer and target it effectively. And so, from our learnings from our phase I trial at City of Hope, we're thinking that combinatorial therapies may be key.

We know that single agent therapies, maybe in the advanced stage of every solid tumor, may not be as effective. So, building rational combination therapies will be key, and that's what we're doing in our next stage of our clinical program. And also trying to rewire this tumor microenvironment, which, again, is immunologically cold. And so, building things that we can intrinsically engineer into those T-cells because we have the opportunity to be able to engineer these immune cells with almost anything we dream of and making it more effective, survive better in this harsh tumor microenvironment, and produce more anti-tumor responses. And that's the hope for the future.

Alicia Morgans: That's fantastic. So, if you had a final word and could ask for anything, I guess, what would funding do for you in your lab? Where would you go next with this work?

Saul Priceman: Yeah, that's a good question. I mean, we're constantly dreaming. So, PCF was huge for us from the beginning. I mean, clearly, they funded the idea around this and the preclinical laboratory data that supported this trial. And then, the trial itself, which not only allowed us to build a program around developing immunotherapies for prostate cancer, but also is supporting young investigators in my lab and also has allowed us to compete for other funding mechanisms that are building around this idea of CAR T-cell therapy and other immunotherapies for prostate cancer. And so, we're constantly learning. We're taking our learnings from patients and understanding if they responded, why? And if they didn't respond, how do we improve that? And so, I think it's a small iteration each time we go into the clinic, and ideally building an effective therapy.

Alicia Morgans: Well, we are all looking forward to that. And I am eager to see the way that you and your lab continue to shape the field and really provide new opportunities for our patients with prostate cancer. Thank you so much for your time and your continued work in this space.

Saul Priceman: Thank you.

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