Next Article in Journal
Radical Decisions in Cancer: Redox Control of Cell Growth and Death
Next Article in Special Issue
Therapeutic Cancer Vaccines in Prostate Cancer: The Quest for Intermediate Markers of Response
Previous Article in Journal
The Dynamics of Developmental and Tumor Angiogenesis—A Comparison
Previous Article in Special Issue
Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer
Cancers 2012, 4(2), 420-441; doi:10.3390/cancers4020420
Review

Immune Response to Sipuleucel-T in Prostate Cancer

, , , , ,  and *
Received: 5 March 2012; in revised form: 2 April 2012 / Accepted: 6 April 2012 / Published: 18 April 2012
(This article belongs to the Special Issue Immune Responses to Human Prostate Cancer)
View Full-Text   |   Download PDF [246 KB, uploaded 18 April 2012]
Abstract: Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients’ own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte-macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for immunotherapy, patient selection and best sequencing with other prostate cancer therapies remain to be determined. A better understanding of immune response may help address these issues.
Keywords: castrate resistant prostate cancer; immunotherapy; biomarkers; sipuleucel-T; immune response castrate resistant prostate cancer; immunotherapy; biomarkers; sipuleucel-T; immune response
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Thara, E.; Dorff, T.B.; Averia-Suboc, M.; Luther, M.; Reed, M.E.; Pinski, J.K.; Quinn, D.I. Immune Response to Sipuleucel-T in Prostate Cancer. Cancers 2012, 4, 420-441.

AMA Style

Thara E, Dorff TB, Averia-Suboc M, Luther M, Reed ME, Pinski JK, Quinn DI. Immune Response to Sipuleucel-T in Prostate Cancer. Cancers. 2012; 4(2):420-441.

Chicago/Turabian Style

Thara, Eddie; Dorff, Tanya B.; Averia-Suboc, Monica; Luther, Michael; Reed, Mary E.; Pinski, Jacek K.; Quinn, David I. 2012. "Immune Response to Sipuleucel-T in Prostate Cancer." Cancers 4, no. 2: 420-441.


Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert