Toxin-based targeted therapy for malignant brain tumors.
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2012-01
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Abstract
Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy-the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages.
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Chandramohan, Vidyalakshmi, John H Sampson, Ira Pastan and Darell D Bigner (2012). Toxin-based targeted therapy for malignant brain tumors. Clinical & developmental immunology, 2012. p. 480429. 10.1155/2012/480429 Retrieved from https://hdl.handle.net/10161/25632.
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Scholars@Duke
Vidyalakshmi Chandramohan
The research work in my laboratory focuses on identifying novel immunotherapeutic targets for the treatment of brain tumors, specifically glioblastoma (GBM). My previous work includes the development of the dual-specific immunotoxin (IT) D2C7-IT, which is currently in Phase I clinical trials in recurrent GBM (rGBM) patients. My current research seeks to identify novel strategies to enhance the efficacy of D2C7-IT and other GBM-targeted cytotoxic therapies. In conjunction with this, my research includes the investigation of immune-related biomarkers to predict the clinical outcome of D2C7-IT therapy in patients with GBM.
John Howard Sampson
Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratumoral infusion parameters and drug distribution within brain tumors and normal brain.
The Duke Brain Tumor Immunotherapy Program (BTIP) has an emphasis on translational research in Neuro-Oncology. There are two main areas of study. The first is novel mechanisms of delivery of large molecular weight molecules, such as monoclonal antibodies, throughout brain intersitial space using novel intracerebral infusion techniques developed by this laboratory. Studies exploring this technology are undertaken in both small and large laboratory animals and patients with brain tumors.
The other focus of the BTIP is translational immunotherapy. In this line of work, dendritic cell vaccination strategies and adoptive T-cell strategies have been developed to target novel and well-characterized tumor-specific antigens in patients with brain tumors. The BTIP integrates well with and works closely with the Preston Robert Tisch Brain Tumor Center at Duke. The BTIP is well funded and currently holds seven NIH grants, including a SPORE in Brain Cancer grant. There are a large number of investigators at various levels so that students will get exposure to various levels of research and mentorship.
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