Dendritic-cell- and peptide-based vaccination strategies for glioma
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Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments currently being investigated for malignant glioma, immunotherapy is theoretically very attractive, since it offers the potential for high tumor-specific cytotoxicity. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. Therefore, dendritic cell-based immunotherapy could be a new treatment modality for patients with glioma. Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy for malignant glioma.
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The primary goal of cancer vaccines is to activate the immune system to eliminate tumor cells without affecting normal tissues. There are two major approaches to cancer immunotherapy: active immunotherapy and passive immunotherapy (Fig. 1). Active immunotherapy involves the delivery of a substance designed to elicit an immune reaction. The host's immune system must first recognize and then respond to the target. Passive immunotherapy involves the delivery of a substance with intrinsic immunological activity such as an antibody or activated lymphocytes. This chapter focuses on the former approach.
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Malignant glioma is the most common malignant intracranial tumor. Recently, there has been progression in the treatment of malignanr glioma by using dendritic cell(DC) vaccination. It has been proved that the DC vaccination has shown positive effects on malignant glioma. Many studies have reported that DC vaccination can prolong the survival of malignant glioma patients. By loading glioma antigens, the vaccines can effectively reverse the immune suppression induced by glioma cells and activate immune systems to eradiate glioma cells without cousing harmness to normal cells.Therefore, DC vaccination has a promising prospect in the treatment of malignant glioma. The capacity of DC vaccines in the activation of immune systems can be enhanced via choosing antigens of high specificity, modulating regulators in the tumor microenvironment, and regulating molecules expressed on DCs.
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Dendritic cells; Vaccines; Glioma; Immunotherapy; Dendritic cell vaccines tumor microenvironment
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Abstract Conflicts amongst reports concerning the efficacy of both nonspecific and specific attempts at immunotherapy may be ascribed to different animal models utilizing tumors of different immunogenicity. We have selected the B16 mouse melanoma model as the example of a spontaneously occurring neoplasm that is histocompatible with the host and does have tumor‐associated antigens. Attempts to alter tumor growth or survival with nonspecific active immunotherapy as well as with specific active immunotherapy were not successful. Nonspecific active pre‐immunization failed to alter tumor take or growth. Specific active immunotherapy both with and without adjuvant did decrease tumor take and prolong host survival. The effects were increasingly documented at lower tumor cell inoculums and became less apparent with increase in the tumor cell challenge.
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PROBLEM: The immunological mechanism of an effective immunotherapy with paternal lymphocytes for unexplained recurrent spontaneous abortion (RSA) is not yet clear. Previous studies revealed that progesterone plays an important role in maintaining normal pregnancy and lower expression of progesterone receptor (PGR) on lymphocytes was found in RSA. Therefore, it was of interest to investigate whether immunotherapy for RSA would be able to enhance the expression of PGR on lymphocytes of RSA. METHOD: PGR expression on lymphocytes was analyzed with indirect immunofluorescence using flow cytometry. RESULTS: There was no change of PGR expression on PBL of RSA between pre‐ and post‐immunotherapy ( P > 0.05), while in the presence of 10.0 ug/ml progesterone for 24 h, PGR expressed on PBL on post‐immunotherapy was increased significantly as compared with that of pre‐immunotherapy in successful cases ( P < 0.05) and decreased in abortive cases ( P < 0.05). Most PGR was expressed on both CD4 + and CD8 + lymphocyte subsets. In successful cases, CD8 + PGR + subset of post‐immunotherapy was found to be increased significantly ( P < 0.05) in comparison with that of pre‐immunotherapy. CONCLUSION: The data in the present study suggest that immunotherapy for RSA induced a higher expression of PGR on progesterone‐treated lymphocytes, which may be involved in successful pregnancy.
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Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments currently being investigated for malignant glioma, immunotherapy is theoretically very attractive, since it offers the potential for high tumor-specific cytotoxicity. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. Therefore, dendritic cell-based immunotherapy could be a new treatment modality for patients with glioma. In this review, we will discuss the implications of these findings for glioma therapy. A literature review of dendritic cell-based glioma immunotherapy was used to overview the dendritic cell in immunobiology, in the central nervous system and in tumor immunology, glioma-associated antigens, dendritic cell therapy in animal glioma model, dendritic cell therapy in clinical trials and future directions in dendritic cell therapy. Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. Dendritic cell therapy of glioma seems to be safe and without major side effects. Its efficacy should be further determined in randomized, controlled clinical trials. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy for malignant glioma.
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