Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Standard systemic treatment of prostate cancer today is comprised of antihormonal and cytostatic agents. Vaccine therapy of prostate cancer is principally attractive because of the presence of tumor-associated antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), and others. Most prostate cancer vaccine trials have demonstrated some activation of the immune system, limited clinical success, and few adverse effects.One strategy to overcome the problem of limited clinical success of vaccine therapies in prostate cancer could be strict patient selection. The clinical course of patients with prostate cancer (even in those with PSA relapse following surgery or radiotherapy with curative intention, or those with metastatic disease) can vary significantly. In patients with organ-confined prostate cancer, the most promising immunotherapeutic approach would be an adjuvant therapy following surgery or radiotherapy. Patients with PSA relapse following surgery or radiotherapy could also benefit from immunotherapy because tumor burden is usually low. However, most patients in prostate cancer vaccine trials had metastatic hormone-refractory prostate cancer (HRPC). High tumor burden correlates with immune escape phenomena. Nevertheless, 2 years ago, it was demonstrated, for the first time, that a tumor vaccine can prolong survival compared with placebo in patients with HRPC. This was demonstrated with the vaccine sipuleucel-T (APC-8015; Provenge), a mixture of cells obtained from the patient's peripheral blood by leukapheresis followed by density centrifugation and exposition. The Biologics License Application for this vaccine was denied by the US FDA in mid 2007, however, because the trial had failed to reach the primary endpoint (prolongation of time to tumor progression). Nevertheless, clinical trials with sipuleucel-T are ongoing, and the approach still looks promising. Another interesting approach is a vaccine made from whole tumor cells: GVAX. This vaccine is presently being studied in phase III trials against, and in combination with, docetaxel. The results from these trials will become available in the near future. Besides the precise definition of the disease status of patients with prostate cancer, combinations of vaccine therapy with radiotherapy, chemotherapy, and/or hormonal therapy are approaches that look promising and deserve further investigation.
 ...
PMID:Prostate cancer vaccines: current status and future potential. 1834 5

Surgery, radiation and chemotherapy are three major therapies for cancer. But now, hope is being gathered in immunotherapy as a treatment for fourth. Immunotherapy has been done than before, but they are non-specific immunotherapy. Those that have become hot topics are specific immunotherapies targeting certain molecules or antigens. In this chapter, current status and prospects of immunotherapy for castration-resistant prostate cancer (CRPC) are described. As concrete examples, Sipuleucel-T(Provenge), GVAX, PROSTVAC-VF, Ipilimumab (anti-CTLA-4 mAb), anti-PD-1 mAb and anti-PSMA mAb are cited. As a result, it is not obtained results which therapy also satisfactory at present. Because of its uncertainties we are in the developmental stages of this therapy and improved outcomes might be achievable.
 ...
PMID:[Current status and prospects of immunotherapy for castration-resistant prostate cancer]. 2551 54