Michael Platten1,2, Lukas Bunse3,4, Dennis Riehl3,5, Theresa Bunse3,6, Katharina Ochs3,4, Wolfgang Wick4,7. 1. DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, INF 280, 69120, Heidelberg, Germany. michael.platten@umm.de. 2. Department of Neurology, Mannheim Medical Center, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. michael.platten@umm.de. 3. DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, INF 280, 69120, Heidelberg, Germany. 4. Department of Neurology, Heidelberg Medical Center, University of Heidelberg, INF 400, 69120, Heidelberg, Germany. 5. Immune Monitoring Unit, DKTK, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany. 6. Department of Neurology, Mannheim Medical Center, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. 7. DKTK Clinical Cooperation Unit Neurooncology, German Cancer Research Center, INF 280, 69120, Heidelberg, Germany.
Abstract
PURPOSE OF REVIEW: To discuss the current state of glioma vaccine development and highlight the challenges associated with clinical implementation of these approaches. RECENT FINDINGS: Vaccination strategies against gliomas have matured considerably during the past years, although proof-of efficacy from controlled clinical trials is still lacking. Advances in antigen discovery, including the definition of neoepitopes including epidermal growth factor receptor variant III (EGFRvIII), isocitrate dehydrogenase (IDH)1R132H and Histone (H)3.3K27M, using multi-omic approaches and computational algorithms allow targeting single antigens, but also implementing truly personalized approaches. In addition, new concepts of vaccine manufacturing including RNA and DNA vaccines improve immunogenicity and applicability in personalized settings. As an increasing amount of clinical data defy the concept of the central nervous system (CNS) as a strictly immunoprivileged site, novel vaccine approaches enter the clinic including critical efforts to identify biomarkers of response and resistance and strategies to overcome the immunosuppressive glioma microenvironment.
PURPOSE OF REVIEW: To discuss the current state of glioma vaccine development and highlight the challenges associated with clinical implementation of these approaches. RECENT FINDINGS: Vaccination strategies against gliomas have matured considerably during the past years, although proof-of efficacy from controlled clinical trials is still lacking. Advances in antigen discovery, including the definition of neoepitopes including epidermal growth factor receptor variant III (EGFRvIII), isocitrate dehydrogenase (IDH)1R132H and Histone (H)3.3K27M, using multi-omic approaches and computational algorithms allow targeting single antigens, but also implementing truly personalized approaches. In addition, new concepts of vaccine manufacturing including RNA and DNA vaccines improve immunogenicity and applicability in personalized settings. As an increasing amount of clinical data defy the concept of the central nervous system (CNS) as a strictly immunoprivileged site, novel vaccine approaches enter the clinic including critical efforts to identify biomarkers of response and resistance and strategies to overcome the immunosuppressive glioma microenvironment.
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