Review

Immunotherapy of glioblastoma multiforme Keith L Knutson 1, Lupe Salazar, Kathy Schiffman and Mary LDisis

Glioblastoma multilorme is immunogenic and several glioblastoma multiforme-related antigens have now been identified. In addItion, the immunologic characteristics of the tumor microenvironment that may affect tumor growth are becoming increasingly understood. The type of immune-based approach selected to treat glioblastoma multiforme will depend on the tumor burden. For minimal diseose states, active vaccination may be uselullor generating adequate protection from relapse. However, for more advanced stoge disease states, more rigorous strategies may need to be applied, such as adoptive T-cell therapy, anfibody therapy or a combination of different techniques. The immunosuppressive environment observed during advanced malignancy may need to be reversed for improved efficacy of immune-based therapies. Expert Rev. NeurolheIapeutia 3(4), 511-523 (2003) Advances in basic inununology over the past decade have resulted in the development of immune-based therapies for many cancers. Perhaps the most Important advances for glioblastoma multi formes (GBM)s are the understanding that GBM lUmors are immu­ nogenic and the identification of tumor-spe­ cific antigens. Some of the identified tumor antigens are important for malignant transfor­ mation while others enhance growth, metabo­ lism, invasion or metastasis. Immune-based therapies targeting these antigens may result in the eradication of tumor cell clones that drive tbe initiation of malignancy or help eradicate minimal residual disease after apparently suc­ cessful conventional treatments. An under­ standing of the interactions of .he immune system and tumor will greatly influence our approach to the design of immunotherapies. In order to augment the immune response to GBM antigens, not only is the stimulation of both COB cytotoxic T-cen (CTL) and CD4 helper T-cell immunity critically important, but tumor-indul:l'd Immunosupprpsslon must also be overcome. Immune-based therapies are being applied clinically, both for treatment and prevention. Vaccines targeting tumor ant.igens are increaSingly being researched and studied as chemopreventive agents designed to protect

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