An overview of sipuleucel-T Autologous cellular immunotherapy for prostate cancer

Dendreon Corporation, Research, Seattle, WA, USA.
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 04/2012; 8(4):520-7. DOI: 10.4161/hv.18769
Source: PubMed


Sipuleucel-T, the first autologous active cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells (including antigen presenting cells) with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase) and granulocyte-macrophage colony stimulating factor. Treatment consists of 3 infusions at approximately 2-week intervals, resulting in a prime-boost pattern of immune activation, a robust antigen-specific cellular and humoral immune response, and, consequently, a survival benefit in subjects with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Adverse events are generally mild to moderate and resolve within 2 d. Serious adverse events occur at a low rate. As the first autologous cellular immunotherapy to demonstrate a survival benefit, sipuleucel-T is a novel oncologic therapeutic that warrants the reassessment of the current prostate cancer treatment paradigm.

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    • "The rationale for using autologous dendritic cells in cancer immunotherapies is based on their efficient activation of antigen-specific cytotoxic T cells to kill cancer cells. Sipuleucel-T is a dendritic-based immunotherapy in which autologous peripheral blood mononuclear cells (PBMCs) are incubated ex vivo for 36–48 hours with a fusion protein (PA2024) of PAP and granulocyte-macrophage colony-stimulating factor (GM-CSF) [35]. An analysis of culture supernatant during the manufacture process showed an increase in antigen presenting cell (APC) activation cytokines (interleukin (IL)-1a, IL-23, macrophage inflammatory protein (MIP)-1a and -1b), T cell activation markers (IL-2, -3, -4, -5, -10, and -17) as well as APC/T cell activation-associated cytokines (IL-12, IFNγ, tumour necrosis factor (TNF)) [36]. "
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    ABSTRACT: The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.
    BioMed Research International 09/2014; 2014. DOI:10.1155/2014/981434 · 1.58 Impact Factor
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    • "Interest in cancer immunotherapy has been revived with the 2010 US Food and Drug Administration approval of sipuleucel-T, the first approved therapeutic vaccine for the treatment of advanced cancer [1,2]. The recent approval of the CTLA-4 monoclonal antibody ipilimumab has generated further interest in immune-based therapies in cancer [3,4]. "
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    Journal of Translational Medicine 03/2013; 11(1):62. DOI:10.1186/1479-5876-11-62 · 3.93 Impact Factor
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    • "Leukapheresis is common in the stem cell transplant setting for treatment of lymphomas, multiple myeloma, and some solid tumors. The cell therapy Provenge uses leukapheresis to obtain PBMNCs and antigen presenting cells for further manipulation (Wesley et al., 2012). The product of leukapheresis, termed a leukopak, may also contain CTCs. "
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    ABSTRACT: Circulating tumor cells (CTCs) are believed to be responsible for the development of metastatic disease. Over the last several years there has been a great interest in understanding the biology of CTCs to understand metastasis, as well as for the development of companion diagnostics to predict patient response to anti-cancer targeted therapies. Understanding CTC biology requires innovative technologies for the isolation of these rare cells. Here we review several methods for the detection, capture, and analysis of CTCs and also provide insight on improvements for CTC capture amenable to cellular therapy applications.
    Frontiers in Oncology 07/2012; 2:69. DOI:10.3389/fonc.2012.00069
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