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Anti-Prostate Cancer Effects Of Ctl Cells Induction By Recombinant Adenovirus Mediated Psca Dendritic Cells

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2017)

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Abstract
Immunotherapy has shown evidence of efficacy in reducing the risk of death among primary and metastatic tumor patients. In this study, we develop an antitumor vaccination through cytotoxic T lymphocytes (CTL) induction by recombinant adenovirus (Ad) mediated prostate stem cell antigen (PSCA) dendritic cells (DC) for prostate cancer therapy. DC was stimulated to maturity through infecting with Ad carrying PSCA cDNA. After that, Ad(PSCA)-DC utilized to induce CTL for prostate cancer therapy. The results revealed that Ad(PSCA) infection improved DC maturation including the change of morphological and the expression of surface markers. Ad(PSCA) infection up-regulated the secretion of interleukin-12, but down-regulated interleukin-10 secretion. CTL displayed high IFN-gamma secretion level after Ad(PSCA)-DC induced. In vitro, Ad(PSCA)-DC-CTL markedly inhibited PC-3 cell proliferation related to DC-CTL at the effector: target ratio of 20:1. In vivo, Ad(PSCA)-DC-CTL displayed strong prostate cancer cytotoxicity including inhibiting tumor formation, delaying tumor growth and improving mice survival rate. Pathological examination revealed that the numbers of infiltrating Ad(PSCA)-DC-CTL within mice tumor tissues increased relative to DC-CTL. Through further in-depth investigation, the proposed Ad(PSCA)-DC-CTL could serve as an effective anti-tumor immunity strategy against prostate cancer.
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Key words
Prostate cancer, cytotoxic T lymphocytes (CTL), prostate stem cell antigen (PSCA), dendritic cells (DC), adenovirus
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