Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer.

Abstract

As the most common malignancy among North American males, prostate cancer causes more than 30,000 deaths each year. After local and hormonal treatments, a great number of patients ultimately progressed to castrate-resistant prostate cancer (CRPC), in which chemotherapy provides a small survival advantage, but with significant toxicities. In the past decade, prostate cancer has become a target for several immunotherapeutic approaches. Sipuleucel-T (Provenge®, or APC8015) is a novel cancer vaccine developed from autologous dendritic cells (DC) loaded with engineered fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phase I and Phase II trials show that the vaccine is safe and effective in creating immune responses toward the fusion-protein target antigen, PAP-GM-CSF also call PA2024. Recent Phase III studies also demonstrated sipuleucel-T's efficacy in prolonging median survival in patients with CRPC, despite little or no effect on clinical disease progression or surrogates such as serum PSA kinetics. Subsequently, the United States Food and Drug Administration approved sipuleucel-T for the treatment of asymptomatic or minimally symptomatic CRPC in April 2010. Filings are projected with international regulatory agencies in 2011. While the development of sipuleucel-T provides an option for patients with early CRPC, it also introduces physicians and researchers to new unanswered questions regarding its optimal clinical use and questions about mechanism of action and combination and sequencing with other agents.

• Authors: Eddie Thara, Tanya B Dorff, Jacek K Pinski, David I Quinn
• Journal: Maturitas (Maturitas) Vol. 69 Issue 4 Pg. 296-303 (Aug 2011) ISSN: 1873-4111 [Electronic] Ireland
• PMID: 21621934 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Cancer Vaccines
• Tissue Extracts
• Granulocyte-Macrophage Colony-Stimulating Factor
• sipuleucel-T
• Acid Phosphatase
• prostatic acid phosphatase
• Protein Tyrosine Phosphatases

Topics

• Acid Phosphatase
• Cancer Vaccines (immunology)
• Dendritic Cells
• Disease Progression
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology)
• Humans
• Immunotherapy, Active
• Kaplan-Meier Estimate
• Male
• Prostatic Neoplasms (immunology, therapy)
• Protein Tyrosine Phosphatases (immunology)
• Tissue Extracts (immunology)