An overview of sipuleucel-T: autologous cellular immunotherapy for prostate cancer.
ABSTRACT 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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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; · 2.71 Impact Factor
- Clin Exp Vaccine Res. 01/2014; 3:113-116.
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ABSTRACT: Editorial Dendritic cells (DCs) are professional antigen presenting cells, which play a pivotal role in antigen (Ag)-specific T cell immunity. Malignancies have the capacity to inacti-vate DCs and effector T cells or to evade circulating anti-tumor immunity by express-ing immune inhibitory molecules and/or secreting immunosuppressive cytokines. For this reason, ex-vivo-generated DCs  or in-vivo-DC-targeting  has been studied intensively over the past decade or development as a potential therapeutic cancer vac-cine. Understanding how DCs induce, regulate, and maintain T cell immunity is es-sential for the design of novel cancer vaccines with improved clinical efficacy. Once activated, Ag-pulsed DCs are geared toward the launching of Ag-specific immunity, leading to T cell proliferation and differentiation into effector T cells. DCs are also im-portant in triggering humoral immunity partly due to their capacity to directly interact with B cells and to present unprocessed antigens. There are examples of DC-based tu-mor vaccines being used successfully in clinical practice. Sipuleucel-T, the first Food and Drug Administration (FDA)-approved DC vaccine (Dendreoninc.) has been found to be somewhat effective in the treatment of human prostate cancer . As of 2014, 289 clinical studies of DC-based cancer vaccines are registered and under investiga-tion (2014, http://www.clinicaltrials.gov). Among the 289 cases, 2 are in phase IV, 6 in phase III, 3 in phase II&III, 74 in phase II, 76 in phase I&II, 109 in phase I, and 3 in phase 0, underscoring the potential clinical significance of this therapy. In this editori-al, we will discuss the evolution of DC-based cancer vaccine strategy, and future im-plications, with an emphasis on the efficacy and limitations of DC-based vaccine. Bet-ter understanding of DC biology and manipulation of activated DCs will allow DC sci-entists to produce the next generation of highly efficient cancer vaccines for cancer patients. First Generation DC Vaccines For the first generation of DC vaccines, patient-isolated or ex-vivo-generated mono-cyte-derived DCs (MoDCs) were used without additional modifications. Those pri-mary DC vaccines were loaded with tumor lysates, recombinant tumor antigens or synthetic peptides. The early clinical trials of DC vaccines established the safety and feasibility of DC-based cancer vaccines, with relatively lower toxicity when compared with chemotherapy or radiation therapy. However, these unmodified MoDC vaccines only led to a tumor regression rate of 3.3% in patients with cancer. Because of this, pep-tide-loaded DCs were utilized, and demonstrated an improved tumor regression rate © Korean Vaccine Society.