Cell-Mediated Immunotherapy
Cell-Mediated Immunotherapy
Background: The dismal prognosis for patients harboring intracranial gliomas has prompted an intensive search for effective treatment alternatives such as immunotherapy. Our increased knowledge in basic immunology, glioma immunobiology, and molecular biology may lead to the development of effective, rational immunotherapy approaches.
Methods: The authors reviewed the literature on glioma immunology, the status of tumor vaccine therapy and on novel techniques to monitor the tumor-specific immune response.
Results: Experimental conditions currently exist whereby potent antitumor cell-mediated immune responses can be generated. However, clinically, no therapeutic regimen has proven effective. Obstacles to establishing an effective immunotherapy regimen are the lack of a well-defined glioma-specific antigen, the heterogeneity of tumor cells in gliomas, and the modulating effect of the glioma itself on the immune system. Unique strategies to overcome these barriers are being developed.
Conclusions: Novel strategies to generate an anti-glioma immune response through use of dendritic cell vaccination, directed cytokine delivery, gene-based immunotherapy, and reversal of tumor-induced immunosuppression are promising. These strategies carry the potential of overcoming the resistance of gliomas to immunotherapeutic manipulation and, undoubtedly, will become a part of our future therapeutic armamentarium.
Malignant gliomas are the one of the most devastating tumors in current clinical practice. Despite the improvement of local therapies, such as surgery and radiation, the mean survival time for patients carrying a diagnosis of glioblastoma multiforme remains virtually unchanged from a decade ago. On average, patients survive 12 to 18 months, with few patients surviving beyond 2 years. In general, chemotherapy is only marginally effective in the treatment of these lesions due to the difficulty of delivering drugs across the blood-brain barrier and the development of drug resistance by the tumor. Treatment failure in these patients is almost always local, believed to be due in part to the infiltrating nature of the tumor into the surrounding normal white matter. This makes complete surgical resection of these tumors virtually impossible, with a "cure" dependent on the ability to control these infiltrating tumor cells. The poor prognosis for patients with high-grade gliomas has led investigators to seek and develop new and innovative treatment modalities that carry the potential to eradicate these residual infiltrating tumor cells. Tumor vaccine therapy is one such approach. The recognition that lymphocyte infiltration into primary brain tumors is a favorable prognosticator for survival has inspired a variety of approaches to utilize the immune system for the treatment of these tumors. Progress in our under-standing of immunology and molecular biology in general, and specifically glioma immunobiology, has raised hope for the development of an effective vaccine therapy against this aggressive tumor.
Abstract and Introduction
Abstract
Background: The dismal prognosis for patients harboring intracranial gliomas has prompted an intensive search for effective treatment alternatives such as immunotherapy. Our increased knowledge in basic immunology, glioma immunobiology, and molecular biology may lead to the development of effective, rational immunotherapy approaches.
Methods: The authors reviewed the literature on glioma immunology, the status of tumor vaccine therapy and on novel techniques to monitor the tumor-specific immune response.
Results: Experimental conditions currently exist whereby potent antitumor cell-mediated immune responses can be generated. However, clinically, no therapeutic regimen has proven effective. Obstacles to establishing an effective immunotherapy regimen are the lack of a well-defined glioma-specific antigen, the heterogeneity of tumor cells in gliomas, and the modulating effect of the glioma itself on the immune system. Unique strategies to overcome these barriers are being developed.
Conclusions: Novel strategies to generate an anti-glioma immune response through use of dendritic cell vaccination, directed cytokine delivery, gene-based immunotherapy, and reversal of tumor-induced immunosuppression are promising. These strategies carry the potential of overcoming the resistance of gliomas to immunotherapeutic manipulation and, undoubtedly, will become a part of our future therapeutic armamentarium.
Introduction
Malignant gliomas are the one of the most devastating tumors in current clinical practice. Despite the improvement of local therapies, such as surgery and radiation, the mean survival time for patients carrying a diagnosis of glioblastoma multiforme remains virtually unchanged from a decade ago. On average, patients survive 12 to 18 months, with few patients surviving beyond 2 years. In general, chemotherapy is only marginally effective in the treatment of these lesions due to the difficulty of delivering drugs across the blood-brain barrier and the development of drug resistance by the tumor. Treatment failure in these patients is almost always local, believed to be due in part to the infiltrating nature of the tumor into the surrounding normal white matter. This makes complete surgical resection of these tumors virtually impossible, with a "cure" dependent on the ability to control these infiltrating tumor cells. The poor prognosis for patients with high-grade gliomas has led investigators to seek and develop new and innovative treatment modalities that carry the potential to eradicate these residual infiltrating tumor cells. Tumor vaccine therapy is one such approach. The recognition that lymphocyte infiltration into primary brain tumors is a favorable prognosticator for survival has inspired a variety of approaches to utilize the immune system for the treatment of these tumors. Progress in our under-standing of immunology and molecular biology in general, and specifically glioma immunobiology, has raised hope for the development of an effective vaccine therapy against this aggressive tumor.
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