Current Immunotherapeutic Strategies for Central Nervous System Tumors

Abstract

Immunotherapy has emerged as a promising tool in the management of malignant central nervous system (CNS) tumors. Despite the improvement in patient survival, traditional approaches -which consist mostly of surgery, radiotherapy, and chemotherapy -have been largely unsuccessful in permanently controlling these aggressive tumors. Immunotherapeutic strategies therefore offer not only a novel approach, but also an advantage in a way other modalities have been failing. Specifically, the capabilities of the immune system to recognize altered cells while leaving normal cells intact offer tremendous advantage over the conventional therapeutic approaches. This review summarizes our current understanding of immunotherapeutic treatment modalities employed in clinical trials for management of malignant CNS tumors. Keywordsclinical trials; glioma; glioblastoma; immunotherapy; dendritic cells; cytokines; toxins Immune system and the CNSThe immune system has the ability to recognize and destroy foreign cells via two separate modalities: innate and adaptive immunity. The innate component consists of macrophages, natural killer (NK) cells, monocytes, and granulocytes. These cells identify molecular patterns involved in cellular transformation and release various cytokines and inflammatory mediators. The innate response lacks the memory capability for foreign antigens, a feature present in adaptive immune response. This latter component of immune system also features specificity for foreign antigens, imparted by presence of receptors on lymphocytes. Antigen presenting cells (APCs) also play a role in the adaptive response -they engulf foreign antigens and present them to the lymphocytes in the context of major histocompatibility complex. CD4+ T cells Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recent advances in research on antigen presentation, specific cytokines, and T-cell cytotoxicity have given new direction to immunotherapeutic strategies against CNS tumors. Evidence of CNS manifestations after peripheral vaccination with brain-specific antigens in EAE and paraneoplastic cerebellar degeneration models have also lead to a search for possible immunotherapy regimens for management of malignant gliomas [32]. Current directions in immunotherapy investigations include the use of various cytokines, dendritic cells, viral and peptide vaccines, and toxins. NIH Public Access CytokinesCytokines augment T cell activation and MHC antigen expression. Antitumor effects mediated by expression of cytokines in cancer models have been demonstrated with IL-2, IL-4, IL-12, IL-23, IFN-α, and ...

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