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.
    Full-text · Article · Sep 2014 · BioMed Research International
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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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    ABSTRACT: DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. Study 1 -, NCT00250419; Study 2 -, NCT00647114.
    Full-text · Article · Mar 2013 · Journal of Translational Medicine
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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.
    Full-text · Article · Jul 2012 · Frontiers in Oncology
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