Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendreon (formerly Activated Cell Therapy), in association with the Mayo Clinic, is developing the dendritic cell therapy APC-8015 (Provenge) for the potential treatment of hormone-refractory prostate cancer [284376]. Phase III trials were initiated in January 2000 [353557], and in July 2001 Dendreon anticipated that preliminary results would be available by the end of the year [417283], [427591]. As of September 2001, Dendreon was planning tofile a BLA in 2002 [421356]. Provenge involves the use of a proprietary recombinant antigen derived from prostatic acid phosphatase, found in approximately 95% of prostate cancers. The target antigen is combined with the patient's own dendritic cells and reinfused into the patient to stimulate an immune response [406383]. In November 1999, Dendreon received US-05976546, which covers the composition of the prostate tumor antigen engineered by Dendreon to help stimulate the immune system [347885]. In August 2000, Dendreon received US-06080409, entitled 'Immunostimulatory composition', which relates to the method by which Dendreon's vaccines stimulate the T-cell arm of the immune system tofight cancer [379085]. In April 2001, Dendreon was awarded US-06210662 covering the therapeutic composition of APC-8015 [406383].
 ...
PMID:Technology evaluation: APC-8015, Dendreon. 1188 98

Hormonotherapy is the standard treatment for advanced prostate cancer but disease progression ineluctably occurs. Subsequent chemotherapy has a modest symptomatic palliative role even if encouraging results were recently presented with docetaxel and estramustine combination. In this context, there is a great deal of interest in using dendritic cells therapeutically, as they are the most potent professional antigen-presenting cells in the immune system. Based on their unique adjuvant capacity, two vaccinal strategies are therefore tested in clinical trials. First approach includes the administration of cancer cells transduced by a cytokine gene to stimulate the in vivo recruitment and activation of dendritic cells, and the most advanced studies use GM-CSF gene-transduced allogenic cells. The second approach consists in infusions of dendritic cells loaded ex vivo with relevant tumoral antigens. Two prostate antigens have already been used. PSMA evaluated in 130 patients and a fusion protein PAP-GM-CSF (Provenge) in 144 patients. All treatments were well tolerated and frequently generated weak specific responses, but resulted in a limited clinical efficacy. However, engineering of dendritic cells can provide optimised cell vectors able to amplify vaccine response and clinical efficacy.
 ...
PMID:[Cell therapy and prostate cancer]. 1460 63

Prostate cancer is an excellent target for an active vaccine-based approach based on the fact that prostate cancer cells express unique proteins which serve as highly specific targets. APC8015 (Provenge) is one such investigational therapeutic vaccine that uses autologous antigen presenting cells (APCs) loaded with a recombinant fusion protein of prostatic acid phosphatase linked to a molecule that specifically targets a receptor expressed on the surface of human APCs. Clinical trial outcomes have demonstrated activity in patients with androgen independent prostate cancer.
 ...
PMID:Immunotherapy with autologous antigen presenting cells for the treatment of androgen independent prostate cancer. 1564 27

Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure of initial treatment, as indicated by rising prostate-specific antigen (PSA) levels, second-line hormonal therapy is usually instituted. Over the past several years, it has become increasingly clear that systemic chemotherapy has an important role in hormone-refractory disease. Phase II trials have demonstrated high PSA and measurable disease response rates with taxane single-agent and combination treatments. One recent phase III trial showed that docetaxel (Taxotere)/ estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone (Novantrone) plus prednisone. Another phase III trial demonstrated that docetaxel given every 3 weeks plus prednisone significantly improved overall survival, PSA response rate, pain relief response rate, and quality of life compared with mitoxantrone and prednisone. On the basis of these findings, every-3-week docetaxel plus prednisone is now considered standard first-line therapy for metastatic hormone-refractory disease. There is considerable optimism that treatment can be further improved. Studies of taxane combinations with bevacizumab (Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisense Bcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptor inhibitors, and KDR inhibitors are under way. Randomized phase III trials in progress or planned are examining docetaxel in combination with imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisone in combination with bevacizumab and an antisense clusterin compound. Other promising systemic agents include epothilones and atrasentan, and promising vaccines include Provenge, GVAX, and Prostvac.
 ...
PMID:Recent progress in management of advanced prostate cancer. 1594 43

Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and DN 1924, as well as other HLA-DR antibodies not being developed by Kirin. Previously, in May 1999, Dendreon and Kirin established a collaboration for the development of dendritic cell-based immunotherapeutics for cancer, including Sipuleucel-T. Under the agreement, Kirin would provide financial support for Dendreon's research on dendritic cells focused on developing immunotherapies for cancers most prevalent in Asia. Dendreon would retain US rights to products arising from the collaboration while Kirin would hold the rights to such immuno-therapeutics in Asia and Oceania. In August 2005, Dendreon signed an agreement to lease a commercial manufacturing facility in Hanover, New Jersey, USA. The company intends to develop the facility to meet anticipated clinical and commercial demands of Sipuleucel-T as well as other active immunotherapy product candidates. Dendreon and Diosynth Biotechnology (Akzo Nobel) have an agreement for the commercial production of the PA 2024 antigen component of Sipuleucel-T. In November 2003, Dendreon announced that Diosynth successfully manufactured PA 2024 on a commercial scale. In October 2001, Dendreon announced that Gambro Healthcare Inc. would provide a network of centres for cell collection to support commercial production and clinical development of various Dendreon vaccines, including Sipuleucel-T. Dendreon has outsourced its cell processing operations in Mountain View, California, USA to Progenitor Cell Therapy under an amended agreement signed in August 2002. This agreement is an expansion of an existing agreement, under which Progenitor provided Dendreon with cell-processing services through its facility in Hackensack, New Jersey, USA. The pivotal, two-stage, phase III trial (D9902 study) has been initiated at clinical sites in the US. The first stage of the trial (D9902A study) is a double-blind, placebo-controlled phase III trial designed to evaluate Sipuleucel-T in men with asymptomatic, metastatic, androgen-independent prostate cancer. The trial was originally designed to be the companion study to a previously completed phase III trial, called D9901. However, the D9902A study with 98 patients recruited was halted in December 2002, when analysis of the D9901 study revealed no statistically significant benefit in time to disease progression in the overall group, although a benefit was seen in a subgroup of patients with Gleason scores of < or =7. In April 2002, the US FDA requested clarification regarding cellular composition of Sipuleucel-T and the suspension of additional patient enrollment for the D9902 study; the request was related solely to manufacturing issues without patient safety being an issue. Trial enrollment resumed in October 2002 following FDA authorisation. Dendreon amended the protocol for the D9902 study and is only recruiting patients with asymptomatic, metastatic, androgen-independent prostate cancer, regardless of their Gleason Score (D9902B study). The ongoing pivotal phase III trial underwent a Special Protocol Assessment (SPA) with the FDA in August 2003 and is enrolling approximately 500 patients. The primary endpoint is overall survival with time to objective disease progression being a secondary endpoint. Final 3-year survival analysis of the D9902A study has been completed and presented. Previously, Dendreon completed an earlier phase III trial (D9901 study) that assessed Sipuleucel-T among 127 patients with late-stage, metastatic, hormone-independent prostate cancer in the US. All subjects had undergone surgical resection of the prostate, but had rising levels of PSA. Final 3-year survival data have been reported. Dendreon also conducted a phase II trial, known as D9905, that investigated Sipuleucel-T monotherapy among patients with early-stage prostate cancer. Study findings have been reported. In September 2003, the FDA designated Sipuleucel-T as a fast-track development programme for the treatment of asymptomatic, metastatic, androgen-independent prostate cancer. Subsequently, the FDA granted fast-track status to the vaccine in November 2005. Dendreon announced in September 1999 that a phase I trial of Sipuleucel-T in patients with prostate cancer had commenced in Japan. This study was being conducted at a dendritic cell processing centre that was formed as part of Dendreon's collaboration with Kirin. In addition, the US NCI is conducting a phase II trial (P-16) of Sipuleucel-T in combination with bevacizumab among patients with hormone-dependent prostate cancer. Trial results have been announced. In April 2001, Dendreon was awarded a US patent (No. 6,210,662) covering the composition of Sipuleucel-T. Dendreon acquired an exclusive worldwide licence to dendritic cell therapy for cancers and other diseases from the Immune Response Corporation; Immune Response originally received the exclusive patent rights to the technology from the University of Brussels in Belgium.
 ...
PMID:Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon. 1675 45

Classically, advanced prostate cancer has been treated with hormonal therapy and, most recently, chemotherapy. This treatment clearly demonstrated a survival benefit, but never a cure. With the ever-expanding understanding of the pathophysiology of prostate cancer, there has been a recent explosion in the potential molecular targets and novel therapeutic approaches to both advanced and potentially localized prostate cancer. This review will focus on what the author perceives to be the most promising of these new strategies. The endothelin pathway has been identified as pivotal in the viscous cycle of tumorigenesis in bone, leading to the development of endothelial receptor antagonists. Vaccine therapy using autologous granulocyte-macrophage colony-stimulating factor-producing prostate cancer cells has been effective in producing both immune and clinical responses. Randomized clinical trials of the immunotherapy cell product APC8015 (Provenge) have demonstrated improved survival in the hormone-refractory setting. The development of antisense oligonucleotides to segments of mRNA critical to the progression to androgen-independent disease has emerged as one further tool in the expanding armamentarium of potential therapies being tested. Clearly, headway is being made in improving outcomes in this most prevalent health problem.
 ...
PMID:New molecular targets in advanced prostate cancer. 1683 Oct 72

Dendritic cells from patients with cancer are deficient in number and functional activity, leading to inadequate tumor immunosurveillance as a result of poor induction of T-cell antitumor responses. Loaded dendritic cell therapy is a vaccination strategy aimed at eliciting tumor antigen-specific, T-cell immune responses. Loaded dendritic cell therapy using prostatic acid phosphatase (APC8015; Provenge, Dendreon Corp., Seattle, WA) as an immunogen has shown a survival benefit in patients with metastatic hormone-refractory prostate cancer in a randomized phase III trial. This review will summarize the prostate cancer clinical trials using APC8015 and discuss the potential future role of APC8015 in prostate cancer treatment.
 ...
PMID:Immunotherapy for prostate cancer using prostatic acid phosphatase loaded antigen presenting cells. 1696 96

Sipuleucel-T (Provenge; APC8015; Dendreon Corp, WA, USA) is a novel immunotherapeutic cellular product, which includes autologous dendritic cells pulsed ex vivo with a recombinant fusion protein (PA2024) consisting of granulocyte macrophage colony-stimulating factor and prostatic acid phosphatase. Two Phase II trials in men with androgen-dependent biochemically relapsed prostate cancer have demonstrated a decrease in prostate-specific antigen and prolongation in prostate-specific antigen doubling time. In men with hormone-refractory prostate cancer, clinical trials have demonstrated both biological activity and clinical response to sipuleucel-T. Data from two Phase III trials in men with asymptomatic, metastatic hormone-refractory prostate cancer demonstrated an improved median overall survival in men who received sipuleucel-T compared with placebo. Clinical trials are ongoing or are being developed to evaluate sipuleucel-T in various prostate cancer disease states and in combination with other treatment modalities.
 ...
PMID:Sipuleucel-T (APC8015) for prostate cancer. 1702 Apr 51

Dendritic cells are deficient both in number and function in patients with cancer. Loaded dendritic cell therapies aim to overcome this deficiency by delivering antigens to antigen-presenting cells under ex vivo conditions, improving dendritic cell function. APC8015 (Provenge; Dendreon Corp., Seattle, WA) is a novel immunotherapeutic, which consists of autologous dendritic cells pulsed ex vivo with PA2024, a recombinant fusion protein consisting of granulocyte macrophage colony-stimulating factor and prostatic acid phosphatase, as an immunogenic agent. A Phase III randomized clinical trial has demonstrated a survival benefit in patients with metastatic hormone-refractory prostate cancer. This review summarizes the clinical trials using APC8015 in prostate cancer and discusses its future role in the treatment of prostate cancer.
 ...
PMID:Immunotherapy for prostate cancer using antigen-loaded antigen-presenting cells: APC8015 (Provenge). 1769 25

(1) Sipuleucel-T (Provenge) is an active cellular immunotherapy (therapeutic vaccine) that is designed to stimulate the patient's T-cells to recognize and attack prostate cancer cells that express prostatic acid phosphatase (PAP) antigen. (2) Sipuleucel-T demonstrated a survival benefit in men with advanced androgen-independent prostate cancer (AIPC), although this preliminary finding requires confirmation in larger trials. (3) Mild to moderate myalgia, chills, fever, and tremor are the most commonly reported adverse events for patients receiving sipuleucel-T. These events generally resolve quickly. (4) More studies are needed to evaluate sipuleucel-T in the earlier stages of prostate cancer and in combination with conventional therapies.
 ...
PMID:Sipuleucel-T (Provenge): active cellular immunotherapy for advanced prostate cancer. 1776 75


1 2 3 4 Next >>