Current status of immunological therapies for prostate cancer.
OBJECTIVE
Considerable progress has been made in prostate cancer immunotherapy over the last year, and two agents have completed phase III testing. This review will discuss the most promising immune-directed strategies in development for prostate cancer, outlining interventions that mitigate tumor-induced tolerance and highlighting several combination immunotherapy approaches.


RESULTS
A pivotal phase III study using Sipuleucel-T, an autologous prostatic acid phosphatase (PAP)-loaded dendritic cell immunotherapy, in men with metastatic castration-resistant prostate cancer (CRPC) demonstrated a survival advantage over placebo. By contrast, two phase III studies of GVAX, an allogeneic tumor cell vaccine, in a similar patient population failed to show a survival benefit of GVAX or GVAX/docetaxel over standard docetaxel/prednisone. Other strategies currently in clinical development include the ProstVac poxviral vaccine, a PAP-encoding DNA vaccine, and immune checkpoint inhibitory approaches.


CONCLUSIONS
Although Sipuleucel-T may receive FDA approval for patients with metastatic CRPC, challenges remain in identifying immunotherapy strategies that overcome immune tolerance, especially when disease burden is substantial. An emerging paradigm focuses on using immunotherapy together with checkpoint antagonists or in combination with conventional therapies in patients with early-stage disease. Such approaches are likely to yield optimal results, but must carefully be explored in well designed phase II studies before moving forward.
Antonarakis
Emmanuel S
ES
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.
Drake
Charles G
CG
D019496:Cancer Vaccines / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods* / Q000639:trends*; D008297:Male; D011471:Prostatic Neoplasms / Q000628:therapy*; D014020:Tissue Extracts / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000627:therapeutic use
D019496:Cancer Vaccines; D007155:Immunologic Factors; D014020:Tissue Extracts; D019444:Vaccines, DNA; C511774:sipuleucel-T