title: Development of sipuleucel-T: autologous cellular immunotherapy for the treatment of metastatic castrate resistant prostate cancer.
abstract: Sipuleucel-T, the first autologous 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 autologous antigen presenting cells (APCs), with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase [PAP]) and granulocyte colony-macrophage stimulating factor (GM-CSF). A full course of treatment comprises 3 infusions of sipuleucel-T, given at approximately 2-week intervals. The pattern of APC activation is consistent with priming by the first infusion, and boosting by the second and third infusions. Preclinical and clinical studies have demonstrated evidence of a robust antigen-specific immune response that includes a progressive and persistent increase in antigen-specific cellular and humoral immune responses. Treatment with sipuleucel-T has demonstrated a survival benefit in Phase 3 studies of subjects with metastatic castrate resistant (hormone refractory) prostate cancer (mCRPC). Adverse events with sipuleucel-T were generally mild to moderate and resolved within 2 days. Serious adverse events, autoimmune events, and cerebrovascular events occurred at a similar rate to control subjects. As the first autologous cellular immunotherapy to demonstrate an improvement in overall survival in asymptomatic or minimally symptomatic mCRPC patients, sipuleucel-T represents a new treatment paradigm in oncology.
authors: Dendreon Corporation, 1301 Second Avenue, Suite 3200, Seattle, WA 98101, Seattle, WA 98121, USA. rsims@dendreon.com
authors: Robert B
authors: RB
authors: Sims
mesh_terms: D000135:Acid Phosphatase; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009362:Neoplasm Metastasis; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D014020:Tissue Extracts / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014020:Tissue Extracts; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C511774:sipuleucel-T; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases