Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.
Highlights
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor in the central nervous system (CNS) in adults [1]
In GBM, isocitrate dehydrogenase 1 (IDH1) mutations can predict whether the tumors are secondarily developed from lower-grade gliomas because IDH1 mutations are rarely found in primary GBM
A subsequent open-label phase II multicenter clinical trial in surgically resectable recurrent GBM (rGBM) patients treated with HSPPC-96loaded antigens, which were extracted from patient-derived glioma tissue, showed an impressive median overall survival (OS) of 42.6 weeks and a 6-month OS of 29.3%, respectively [26]
Summary
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor in the central nervous system (CNS) in adults [1]. A subsequent open-label phase II multicenter clinical trial in surgically resectable rGBM patients treated with HSPPC-96loaded antigens, which were extracted from patient-derived glioma tissue, showed an impressive median OS of 42.6 weeks and a 6-month OS of 29.3%, respectively [26] These results have sparked multiple ongoing clinical trials: NCT00905060, a completed phase II trial exploring the application of autologous HSPPC-96 following tumor resection and adjuvant RT and TMZ in ndGBM, and NCT01814813, a multi-institutional trial investigating the safety, tolerability, and efficacy of HSPPC-96 combined with bevacizumab in rGBM patients. Cytomegalovirus phosphoprotein 65 RNA (CMV pp65) is incorporated into DC vaccines because CMV nucleic acids and proteins are found in both primary and recurrent GBM [30] In another phase I trial, patients with ndGBM were administered pp65-specific DCs in combination with preconditioning using tetanus-diphtheria toxoid (Td).
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