Original article

Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 137-147

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer

  • Nadeem A. SheikhAffiliated withDendreon Corporation Email author 
  • , Daniel PetrylakAffiliated withDepartment of Medicine, Columbia University
  • , Philip W. KantoffAffiliated withDana–Farber Cancer Institute, Harvard Medical School
  • , Corazon dela RosaAffiliated withDendreon Corporation
  • , Frances P. StewartAffiliated withDendreon Corporation
  • , Ling-Yu KuanAffiliated withDendreon Corporation
  • , James B. WhitmoreAffiliated withDendreon Corporation
  • , James B. TragerAffiliated withDendreon Corporation
  • , Christian H. PoehleinAffiliated withDendreon Corporation
    • , Mark W. FrohlichAffiliated withDendreon Corporation
    • , David L. UrdalAffiliated withDendreon Corporation



Sipuleucel-T, the first FDA-approved autologous cellular immunotherapy for treatment of advanced prostate cancer, is manufactured by activating peripheral blood mononuclear cells, including antigen presenting cells (APCs), with a fusion protein containing prostatic acid phosphatase. Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses, and to relate the immunological responses to overall survival (OS).


Sipuleucel-T product characteristics [APC numbers, APC activation (CD54 upregulation), and total nucleated cell (TNC) numbers] were assessed in three randomized, controlled phase 3 studies (N = 737). Antigen-specific cellular and humoral responses were assessed in a subset of subjects. The relationships between these parameters and OS were assessed.


APC activation occurred in the first dose preparation [6.2-fold, (4.65, 7.70); median (25th, 75th percentile)] and increased in the second [10.6-fold (7.83, 13.65)] and third [10.5-fold (7.89, 13.65)] dose preparations. Cytokines and chemokines associated with activated APCs were produced during the manufacture of each dose; T-cell activation-associated cytokines were detected in the second and third dose preparations. Antigen-specific T cells were detectable after administration of the first sipuleucel-T dose. Cumulative APC activation, APC number, and TNC number correlated with OS (P < 0.05). Antigen-specific immune responses were observed in 78.8 % of monitored subjects and their presence correlated with OS (P = 0.003).


Sipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo. These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS.


Prostate cancer Cellular Humoral Immunotherapy Survival