Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that several DNA fragments from human prostate-specific membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human prostate-specific antigen (hPSA) genes were selected and fused to create a novel hPSM-mPAP-hPSA fusion gene (named 3P gene), and human secondary lymphoid tissue chemokine (SLC), 3P, and human IgG Fc genes were inserted into pcDNA3.1 to construct a DNA vaccine, designated pSLC-3P-Fc. In this report, to establish a more efficient treatment for immunotherapy against prostate cancer, the construct was transfected into B16F10 to generate gene-modified tumor cell vaccine (named B16F10-SLC-3P-Fc). In poorly immunogenic B16F10 mouse melanoma model, the immunization with B16F10-SLC-3P-Fc resulted in a strong antitumor response and 50% of tumor-bearing mice achieved long-term survival (>120 days). In vivo depletion of lymphocytes indicated that CD8(+) T cells were involved in the direct tumor killing, whereas CD4(+) T lymphocytes were required for the induction of CD8(+) CTL response in B16F10-SLC-3P-Fc-immunized mice. Splenocytes from B16F10-SLC-3P-Fc-immunized mice specifically recognized and lysed PSM, PAP, PSA, and 3P expressing tumor cells. The combined therapy of B16F10-SLC-3P-Fc plus anti-B7-H1 MAbs further enhanced the immune response. Rechallenge experiment showed that a persistent memory response was successfully induced by the combined therapy. These observations suggest pSLC-3P-Fc-modified tumor cells could serve as a vaccine against prostate cancer, and the therapy combined with anti-B7-H1 MAbs further enhanced the antitumor immune response.
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PMID:Potent systemic antitumor immunity induced by vaccination with chemotactic-prostate tumor associated antigen gene-modified tumor cell and blockade of B7-H1. 1718 Apr 70

Dendritic cells play a pivotal role in immune induction. Dendritic cells perform antigen uptake, processing and presentation to T cells only when they are matured and in the functional state. In the development of a vaccine, it is of utmost importance to consider how to make dendritic cells' functions immunologically adequate. In this paper, we report the development of a series of antitumor DNA vaccines with similar structural framework, in which a gene encoding tumor-associated antigenic peptide is ligated upstream to the gene coding secondary lymphoid-tissue chemokine and downstream to the gene encoding the Fc portion of IgG (named chemotactic-antigen DNA vaccine [CADV]). CCR7(+) T, B, natural killer and dendritic cells can be attracted by secondary lymphoid-tissue chemokine, and Fc facilitates antigen uptake via Fc receptors expressed on dendritic cells. In a series of experiments in mice vaccinated by CADV with such tumor-associated antigenic specificities as HPV-16 E7, PSA-PSM-PAP, HER-2/neu, p53 and hTERT, CADV can attract immune cells to the vaccine inoculation site, remarkably inhibit tumor growth and extend survival time in tumor-bearing mice. The antitumor effect is more efficacious than that in mice treated with SLC-Ag or Ag-Fc hybrid gene. Tumor-associated antigenic-specific cytotoxic T lymphocytes can be induced by in vitro experiment in a human system. When combined with measures blocking the negative immune feedback circuits, the therapeutic effect of the vaccine can be further enhanced. Large-scale production of CADV is possible for clinical application.
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PMID:Novel chemotactic-antigen DNA vaccine against cancer. 1840 41