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Investigational All-in-One CAR T-Cell Platform for Prostate Cancer - Nour Shobaki

December 1, 2025

Zachary Klaassen speaks with Nour Shobaki about an all-in-one CAR T-cell platform for metastatic castration-resistant prostate cancer. Dr. Shobaki explains the approach targets STEAP2, a highly prostate-specific antigen, while the CAR T-cells function as living drug delivery systems secreting PSMA CD28 bispecifics locally at tumor sites to activate bystander T-cells against PSMA-positive tumors. The platform also armors CAR T-cells with dominant negative TGF beta receptor 2 to enhance survival in the immunosuppressive tumor microenvironment. Dr. Shobaki indicates the team has identified promising lead constructs from preclinical studies and expects to move toward clinical application following successful IND-enabling studies.

Biographies:

Nour Shobaki, PharmD, PhD, Director of Research, Head of The BRITE Lab, PCF Investigator, The University of Pennsylvania, Philadelphia, PA

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA



Related Content:

ASCO GU 2025: Prevalence of Adverse Events Following T-Cell Engaging Bispecific Antibodies (bsAbs) and Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Metastatic Castrate-Resistant Prostate Cancer (mCRPC): A Meta-Analysis.

PSMA-Targeted Immunotherapy: CAR T and Bispecific T Cell Engagers "Presentation" - Tanya Dorff

Considerations for Patient Selection and Imaging in PSMA-Targeted Therapy - Tanya Dorff & Julie Graff
Read the Full Video Transcript

Zachary Klaassen: Hi. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are at the 32nd PCF Scientific Retreat in Carlsbad, California. I'm delighted to be joined on UroToday by Nour Shobaki, who is a director of basic science research at Penn, and she's one of the young investigators for PCF. She's going to be talking to us today about the all-in-one living CAR T-cell platform. Thanks so much for joining us on UroToday.

Nour Shobaki: Absolutely. It's my pleasure, and thank you so much for having me today.

Zachary Klaassen: It's great to have you. Congratulations on the award. I know you guys gave talks on your updates yesterday at PCF. Just tell us, just for background for our listeners, what is CAR T-cell, and what platform are we talking about?

Nour Shobaki: Absolutely. CAR T-cell therapy is a type of immune therapy. It of course can be used to treat cancer and also other challenging diseases. It involves collecting the blood from the patient, isolating a type of immune cells called T cells, educating them and genetically engineering them to express CAR, which can be selectively targeting specific antigens either expressed on cancer or other diseases, and then infusing back CAR T-cell therapy to patients. This would hopefully boost the immune response against cancer and any other challenging diseases that we are targeting. It can be also other immune diseases or infectious diseases.

Zachary Klaassen: Perfect background. I love that. Tell us about your YI award. You've been working on it for a couple years now. What findings have you found from your work?

Nour Shobaki: We aim to develop safe and effective CAR T cells for prostate cancer. In particular, we are trying to target an advanced stage of prostate cancer referred to as mCRPC, or metastatic castration-resistant prostate cancer, which is an advanced stage that usually spreads to the bone and becomes resistant to therapy. Therefore, of course there is an urgent need to develop new immune therapies that can give hope to patients and their families. We aim to develop an all-in-one living drug CAR T-cell platform to tackle the different challenges in treating solid tumors. As you know, CAR T-cell therapy has shown really remarkable success in blood cancers and hematologic malignancies, but there are some remaining challenges to treat solid tumors, including mCRPC, which is considered a cold tumor microenvironment that does not respond to not just traditional therapy, but even to immune therapy. We're really interested always in my research. During my PhD or postdoc, I'm always interested in the idea of a magic bullet therapy that can actually target the tumor or the target tissue without harming healthy tissues and inducing systemic toxicities.

Our platform is an all-in-one platform. We aim to develop CAR T cells that target STEAP2, which is a highly prostate cancer-associated antigen. Hopefully that would minimize on-target off-tumor toxicities, and then they would serve as living drug delivery systems. They would secrete PSMA CD28 bispecifics locally in the tumor site, and this would activate bystander T cells to eliminate PSMA-positive tumors and STEAP2-negative tumor escape variants, so that we can actually attack different antigens in the same setting. We also armor our CAR T cells with dominant negative TGF beta receptor 2, and this would inhibit TGF beta signal, which is very immune-suppressive, and hopefully this can prolong the survival and longevity of CAR T cells in this hostile TME. We think that this strategy may minimize and overcome several challenges in treating solid tumors at once.

Zachary Klaassen: That's great. I think you mentioned, so STEAP2 is the target?

Nour Shobaki: Yes.

Zachary Klaassen: STEAP1 we just heard about, with AMG 509. This is almost like the next step and a little bit more specific, a different target than STEAP1. Is that correct?

Nour Shobaki: Yes. They are all the same family. STEAP is a family of four, STEAP1, 2, 3 and 4. Of course there are maybe advantages and disadvantages of targeting each one, and I'm sure that some of them are more specific tissues or specific cancer types.

Zachary Klaassen: Sure.

Nour Shobaki: I think that STEAP2 is also highly expressed in breast cancer as well as pancreatic cancer, so it can be also used to target other cancer types, but as far as we know, that it has a very high clean expression and prostate-specific, so hopefully we can minimize toxicities.

Zachary Klaassen: That's great. As a clinician, we know this beautiful work's going on behind the scenes for years and years and years. The question we always have is how far are we away from a Phase I trial, starting to get this into the clinical trial setting?

Nour Shobaki: I think we are very close.

Zachary Klaassen: Good.

Nour Shobaki: We're making small achievements, but it's okay because this is the nature of science, and we're always trying to overcome the challenges we're having with clinical trials. For example, PSMA CAR T cells showed really nice and remarkable success in mCRPC patients when it comes to response and PSA decline, but unfortunately it was also associated with toxicities like CRS and macrophage activation syndrome, or HLH and neurotoxicity. I think, overcoming those types of toxicities with next-generation CAR T cells, hopefully we can make better progress. We already identified nice designs and lead constructs from our in vitro and in vivo studies with this platform, and hopefully we can move forward with clinical application after conducting all our successful IND studies.

Zachary Klaassen: Awesome. I guess just to wrap things up, what's next up in the lab? What's the future directions over say the next couple of years as you wrap up the award?

Nour Shobaki: Thanks to PCF ... we're supported by PCF for two years and even more with other awards in the lab ... we're expanding. I think the platform of CAR T-cell-secreting bispecifics has potential. You can always change the target. You can change the bispecific design to treat and target not just tumor cells, but even modifying the immune compartment and target other tissues. We are now building a team to build on this success, and hopefully we can build on this foundational study and have more future applications not just in prostate cancer, but even other solid tumors as well.

Zachary Klaassen: That's great. Congratulations on just the awesome work and for a great presentation yesterday. Maybe a concluding statement or take-home message for our listeners?

Nour Shobaki: Well, I think the future is, for immunotherapy and the future for CAR T-cell therapy, the future also for in vivo CAR T-cell therapy, so that we can maybe provide patients worldwide with this novel treatment that can be accessible by patients worldwide. What we know from CAR T-cell success in blood cancers is that it's impressive. It can have a long-term remission in patients and can persist in the body for too long. Therefore, I think if we just understand solid tumors and we can tweak our CAR T cells in a way that can overcome current challenges, I think there is so much hope in the future.

Zachary Klaassen: That's great. Nour, a great conversation. Thanks for joining us on UroToday to discuss it.

Nour Shobaki: Absolutely. Thank you so much for having me.