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)

In order to provoke an immune response, a tumor vaccine should not only maximize antigen-specific signals, but should also provide the necessary "co-stimulatory" environment. One approach is to genetically manipulate tumor cells to either secrete lymphokines (GM-CSF, IL-12, IL-15) or express membrane bound molecules (CD80, CD86). Furthermore, patient dendritic cells can be loaded with tumor-associated antigens or peptides derived from them and used for immunotherapy. Genetic modification of dendritic cells can also lead to presentation of tumor-associated antigens. Transfection of dendritic cells with DNA encoding for such antigens can be done in vitro, but transfection efficiency has been uniformly low. Alternatively, dendritic cells can also be modulated directly in vivo either by "naked" DNA immunization or by injecting replication-deficient viral vectors that carry the tumor specific DNA. Naked DNA immunization offers several potential advantages over viral mediated transduction. Among these are the inexpensive production and the inherent safety of plasmid vectors, as well as the lack of immune responses against the carrier. The use of viral vectors enhances the immunogenicity of the vaccine due to the adjuvant properties of some of the viral products. Recent studies have suggested that the best strategy for achieving an intense immune response may be priming with naked DNA followed by boosting with a viral vector. We have successfully completed a phase I and phase II clinical trials on immunotherapy of prostate cancer using naked DNA and adenoviral immunizations against the prostate-specific membrane antigen (PSMA) and phase I clinical trial on colorectal cancer using naked DNA immunization against the carcinoembryonic antigen (CEA). The vaccination was tolerated well and no side effects have been observed so far. The therapy has proven to be effective in a number of patients treated solely by immunizations. The success of the treatment clearly depends on the stage of the disease proving to be most efficient in patients with minimal disease or no metastases. A panel of changes in the phenotype of peripheral blood lymphocytes and the expression of intra-T-cell lymphokines seems to correlate with clinical improvement.
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PMID:In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile. 1141 9

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.
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PMID:[Cell therapy and prostate cancer]. 1460 63