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Specific Antitumor Immune Response Against Prostate Cancer Induced By Prostate Stem Cell Antigen-Pulsed Dendritic Cells

Posted on:2005-05-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:B LiuFull Text:PDF
GTID:1104360125968329Subject:Surgery
Abstract/Summary:PDF Full Text Request
Prostate cancer is the most common cancer and the second leading cause of cancer-related death in American and European male. There is no accurate statistic data about the morbidity and mortality of prostate neoplasm in our country by far. But the number of the patients with prostate cancer rises gradually year by year because of the higher living standard of people and the development of census. It is showed that metastasis occurred in about 30-50 percent of the patients who are firstly diagnosed with prostate cancer. Patients with early stage and localized prostate cancer can be cured by radical prostatectomy or radiotherapy. However nearly one third of the patients with prostate cancer recur with advanced disease after definitive local therapy, including radiation or prostatectomy. Although patients with advanced prostate cancer are effectively treated with androgen ablation, the effect of androgen ablation on disease progression is temporary. These patients ultimately become unresponsive to androgen ablation and are then classified as having hormone-refractory prostate cancer. Therefore the development of novel therapeutic options for the treatment of HRPC needs to be explored in this patient population.Immunotherapy is one of the most important ways in the modern therapy of tumor. With the breakthroughs of tumor immune theory and the development of technology about molecular biology, the concept of tumor vaccine appeared, which is based on the strategy of activating antigen-specific cytotoxic T lymphocytes (CTLs) and effectively inducing anti-tumor immune response. The two key points of this strategy are to seek tumor-associated antigens (TAAs) and how to effectively present antigen. Using antigen- presenting cells (APCs) to present TAAs is the high effective way to activate T cells.Recently, immunotherapy with dendritic cell–based (DC-based) tumor vaccines has emerged as an alternative therapeutic approach for cancer therapy. Multiple studies have used DC-based vaccines to induce tumor immunity, and, in some cases, potent anti-tumor responses have been observed. DCs are the most potent APCs in the immune system. They are critical in the initial recruitment of T cells during immune responses. Although most APCs can present antigen to and activate memory T cells, DCs almost exclusively initiate primary immune responses involving naive T cells. The main function of DCs is to transport antigens from their site of entrance into the body to lymphoid organs, and process the antigen into a form that can be recognized by T cells. DCs then initiate an immune response through the activation of antigen-specific T cells that continually recirculate through lymphoid organs searching for their cognate antigen. The tumor-burdened patients have the character of lacking enough tumor-infiltrated DCs and defecting DC function. Compared with normal DCs, tumor-infiltrated DCs lacks the capability of stimulating the proliferation of T cells. This is one of the leading causes of tumor escaping from immunity. Studies showed that the amount of DCs in prostate cancer tissue was less than 10 percent of the total leucocytes. It was significantly less than that of normal prostate tissue. Recent study found that prostate cancer cells not only kill the mature DCs, but also restrain the proliferation, differentiation and maturation of DCs. It is a new approach for the immunotherapy of HRPC to correct the deficient function of DCs in order to induce and build up the immune reaction of hosts to prostate cancer.The therapy of DC-based vaccine needs to separate DCs from patients' peripheral blood mononuclear cells (PBMCs). Antigen can be delivered to DCs in the form of MHC-restricted peptides, proteins, tumorderived antigenic mixtures, or through transfection with genetic materials, each of which greatly influences the pathway and efficacy of T cell activation by DCs. The optimal strategy for tumor antigen delivery to DCs remains one important aspect that clearly deserves further exploration.Prostate stem cell antig...
Keywords/Search Tags:prostate cancer, prostate stem cell antigen, cytotoxic T lymphocyte, nude mice, dendritic cell, immunotherapy
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