Sipuleucel-T: An innovative immunotherapy option for metastatic castration-resistant prostate cancer

Kelvin A. Moses, MD, PhD

Urology Times® is celebrating its 50th anniversary in 2022. To mark the occasion, we are high-lighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, Kelvin A. Moses, MD, PhD, discusses the prostate cancer treatment sipuleucel-T (Provenge). Moses is an associate professor of urology and fellowship director of urologic oncology at Vanderbilt University Medical Center, Nashville, Tennessee.

Could you provide an overview of sipuleucel-T and how it works in treating prostate cancer?

Sipuleucel-T is a type of immunotherapy, where basically your immune cells are used to fight against cancer. You have cells within your body, called dendritic cells, that are normally quiet. These cells are removed from the body by a process called leukapheresis. And then Dendreon, the manufacturer, basically tags them with a protein that is specific to prostate cancer cells. They are activated, and then they're reinfused back into the patient. It’s almost like a vaccine but using a patient's own cells in order to do that function. This process is repeated twice, for a total of 3 leukapheresis sessions and then 3 infusion sessions in order to complete the entire treatment.

Why should sipuleucel-T be considered an innovation in urology?

The interesting thing about it is that it's not based on the hormonal axis. The vast majority of treatments outside of chemotherapy are based on manipulating the testosterone-hormonal axis, which makes sense because prostate cancer is an androgen-sensitive cancer. But in using an immune therapy approach, and using your own cells, it's very innovative in the mechanism that it works. In that respect, one would consider it quite an innovative therapy.

How would you say sipuleucel-T has improved the treatment of patients with prostate cancer?

For one, it gives patients another option. When this drug first came out, there really were not a lot of options for men with metastatic castration-resistant prostate cancer [CRPC]. There were some toxic chemotherapies that were available, but really not much there. And so it does give patients a non-hormonal option. There is a known survival benefit. It does not have much of a biochemical response, and so the PSA [prostate-specific antigen] really doesn't change very much, or that's not really how you determine responsiveness. The initial study in all patients showed a pretty modest overall survival benefit but consistent with other therapies. But subsequent studies have shown that the earlier that it is given in the metastatic CRPC state, the more effective it is in improving overall survival.

What future innovations are you anticipating in prostate cancer treatment?

The more that we can do personalized treatment, [the better]. Therapies that are based on specific genomic markers in patients is really the future. Some of the immunotherapies that are out there, such as PARP inhibitors or checkpoint inhibitors, are based on certain mutations that patients have. As we get to more specific types of treatments beyond the hormonal axis, there's really the room for improvement and excitement with these personalized genomic-based therapies.