Malignant glioma is usually a deadly disease for which there have

Malignant glioma is usually a deadly disease for which there have been few therapeutic advances over the past century. Introduction A-769662 Each year more than 12 0 new cases of malignant glioma (MG) are diagnosed in the Unites States alone. Gliomas are the most common primary brain tumor and are classified in four types: ependymomas oligodendrogliomas mixed gliomas and astrocytomas. Astrocytomas NAV2 are defined further as grades I through IV becoming progressively more malignant. Stage IV glioma glioblastoma multiforme (GBM) is the most malignant and unfortunately also the most common type of glial tumor. More common than Hodgkin’s disease multiple myeloma and testicular cancer GBM is responsible for more deaths each year than malignant melanoma [1]. Because tumors derive from normal cells they may be difficult to target without incurring substantial collateral damage which in the brain may be debilitating or even deadly. Even with the best available treatment life expectancy for patients with GBM is usually less than 15 months from diagnosis [2]. GBM brain tumors invariably recur and are invariably fatal. In this review we identify 17 reports of glioma immunotherapy clinical trials published between late 2007 and 2009. For the purpose of this review we include only trials that actively involved immune targeting of the tumor or used the patients’ own immune system; therefore we do not include any of the several publications on vascular endothelial growth factor (VEGF)-specific monoclonal antibodies (mAbs). Standard of A-769662 Care Over the years continued improvement in standard-of-care treatment has increased life expectancy for patients with GBM; however even with the best available treatment it remains less than 15 months. Currently the standard of care includes surgical resection followed by radiation therapy (RT) and chemotherapy with temozolomide (TMZ) for newly diagnosed patients with the addition of anti-VEGF mAbs for patients with recurrent disease. Before the introduction of what has become today’s standard therapy the average life expectancy for a patient diagnosed with GBM was even more dismal. One of the early advances in GBM patient treatment was published in 1980 by Walker et al. [3] who exhibited in a randomized clinical trial that patients with newly diagnosed MG treated with RT or RT combined with BCNU (carmustine) survived longer than similar patients not receiving RT. In 1995 Brem et al. [4] reported a survival benefit with BCNU over placebo in patients with recurrent MG. Then in A-769662 2003 Westphal et al. [5] published a phase 3 trial of newly diagnosed MG patients treated with A-769662 either BCNU or placebo and concluded that BCNU also conferred a survival advantage to newly diagnosed patients. Stupp et al. [2] published a phase 3 clinical trial in 2005 in collaboration with 85 institutions in 15 countries evaluating a total of 573 patients with newly diagnosed GBM. Patients were randomly assigned to receive the conventional treatment of resection and RT or resection RT and the addition of TMZ chemotherapy using a 5-day schedule. Patients from all institutions involved in the study exhibited markedly comparable survival rates. Patients who received resection and RT alone survived a median of 12. 1 months whereas those who received resection RT and TMZ survived a median of 14.6 months setting the “gold standard” by which expected survival in newly diagnosed GBM patients is estimated today. In 2006 Stummer et al. [6] exhibited that increasing total tumor resection in MG patients improved survival compared with those left with residual disease. Most recently in 2009 2009 Friedman et al. [7] published results from a clinical trial in which patients with recurrent GBM were treated with the anti-VEGF mAb bevacizumab increasing survival from approximately 6 months to 9.2 months. However although 14.6 months for patients with newly diagnosed GBM and 9.2 months for those with recurrent GBM may be an improvement over previous life expectancy there is still a dire need for further improvement. Tumor Immunotherapy The goal of cancer immunotherapy is usually to take the patient’s own immune system and redirect it to recognize and eliminate tumors with a high degree of specificity. The unique specificity and potency of the immune response directed against tumor targets has the potential to prolong the quality and duration of life or potentially even to cure patients with cancer. In general tumor immunotherapy uses specific antigenic proteins and peptides displayed by tumor cells as targets. Antitumor antibodies may be used either naked or as a platform to deliver.