Acta Biomed. - Vol. 91 - Suppl. 7 - June 2020 | ISSN 0392 - 4203 ACTA BIOMEDICA SUPPLEMENT ATENEI PARMENSIS | FOUNDED 1887 Official Journal of the Society of Medicine and Natural Sciences of Parma and Centre on health systems’ organization, quality and sustainability, Parma, Italy The Acta Biomedica is indexed by Index Medicus / Medline Excerpta Medica (EMBASE), the Elsevier BioBASE, Scopus (Elsevier) and Bibliovigilance Novel therapeutic approaches for tumors of the central nervous system Guest Editors: Salvatore Savasta, Sabino Luzzi Free on-line www.actabiomedica.it Mattioli 1885 1, comma DCB Parma - Finito di stampare June 2020 46) art. Pubblicazione trimestrale - Poste Italiane s.p.a. - Sped. in A.P. - D.L. 353/2003 (conv. in L. 27/02/2004 n. - D.L. 353/2003 (conv. Pubblicazione trimestrale - Poste Italiane s.p.a. Sped. in A.P. ACTA BIO MEDICA Atenei parmensis founded 1887 OFFICIAL JOURNAL OF THE SOCIETY OF MEDICINE AND NATURAL SCIENCES OF PARMA AND CENTRE ON HEALTH SYSTEM’S ORGANIZATION, QUALITY AND SUSTAINABILITY, PARMA, ITALY free on-line: www.actabiomedica.it EDITOR IN CHIEF ASSOCIATE EDITORS Maurizio Vanelli - Parma, Italy Carlo Signorelli - Parma, Italy Vincenzo Violi - Parma, Italy Marco Vitale - Parma, Italy SECTION EDITORS DEPUTY EDITOR FOR HEALTH DEPUTY EDITOR FOR SERTOT Gianfranco Cervellin- Parma, Italy PROFESSIONS EDITION EDITION Domenico Cucinotta - Bologna, Italy Leopoldo Sarli - Parma, Italy Francesco Pogliacomi - Parma, Italy Vincenzo De Sanctis- Ferrara, Italy Paolo Di Benedetto - Udine, Italy Carlo Signorelli - Parma, Italy editorial board Andrea Amerio - Genova, Italy Cosimo Costantino - Parma, Italy Federico Marchesi - Parma, Italy Franco Aversa - Parma, Italy Renato Costi - Parma, Italy Carla Mastrorilli - Bari, Italy Cesare Beghi - Varese, Italy Domenico Cucinotta - Bologna, Italy Tiziana Meschi - Parma, Italy Elena Giovanna Bignami - Parma, Italy Massimo De Filippo - Parma, Italy Jose Luis Navia - Cleveland, OH, USA Riccardo Bonadonna - Parma, Italy Filippo De Luca - Messina, Italy Anna Odone - Milano, Italy David A. Bushinsky - Rochester, NY, USA Vincenzo De Sanctis - Ferrara, Italy Antonio Pellegrino - Lecco, Italy Ovidio Bussolati - Parma, Italy Paolo Di Benedetto - Udine, Italy Silvia Pizzi - Parma, Italy Ardeville Cabassi - Parma, Italy Valentina Fainardi - Parma, Italy Francesco Pogliacomi - Parma, Italy Filippo Cademartiri, Urbino, Italy Claudio Feliciani - Parma, Italy Edoardo Raposio - Parma, Italy Carlo Caffarelli - Parma, Italy Nicola Florindo - Parma, Italy Shaukat Sadikot - Mumbai, India Duran Canatan - Antalya, Turkey Lorella Franzoni - Parma, Italy Simone Cherchi Sanna - New York, NY, USA Fausto Catena - Parma, Italy Antonio Freyrie - Parma, Italy Leopoldo Sarli - Parma, Italy Francesco Ceccarelli - Parma, Italy Federico Fusini - Mondovì (CN) Paolo Schiavi - Parma, Italy Rossana Cecchi - Parma, Italy Vincenza Gianfredi, Milano, Italy Ashraf Tawfic Mohamed Soliman - Doha, Qatar Stefano Cecchini - Parma, Italy Matteo Goldoni - Parma, Italy Mario Strazzabosco - New Haven, CT, USA Gian Paolo Ceda - Parma, Italy Rick Hippakka - Chicago, IL, USA Nicola Sverzellati - Parma, Italy Graziano Ceresini - Parma, Italy Andrew R. Hoffman - Stanford, CA, USA Roberto Toni - Parma, Italy Gianfranco Cervellin - Parma, Italy Joachim Klosterkoetter - Colonia, Germany Frederik H. Van Der Veen - Maastricht, Alfredo Antonio Chetta - Parma, Italy Giuseppe Lippi - Verona, Italy The Netherlands Marco Colonna - St. Louis, MO, USA Wanyun Ma - Beijing, China Vincenzo Vincenti - Parma, Italy Maria Eugenia Colucci - Parma, Italy Umberto Vittorio Maestroni - Parma, Italy Vincenzo Violi - Parma, Italy Paolo Coruzzi - Parma, Italy Marcello Giuseppe Maggio - Parma, Italy Francesco Ziglioli - Reggio Emilia, Italy Lucio Guido Maria Costa - Parma, Italy Pietro Maniscalco, Piacenza, Italy LINGUISTIC ADVISOR EDITORIAL OFFICE MANAGER PUBLISHER Rossana Di Marzio Valeria Ceci Francesco Covino Mattioli 1885 srl Casa Editrice Parma, Italy Mattioli 1885 srl - Casa Editrice Società di Medicina e ­­Scienze Naturali Strada di Lodesana, 649/sx, Loc. Vaio Strada di Lodesana 649/sx, Loc. Vaio Azienda Ospedaliero-Universitaria 43036 Fidenza (PR), Italy 43036 Fidenza (PR), Italy di Parma - Cattani Building, 2nd floor Tel. ++39 0524 530383 Tel. ++39 0524 530383 Via Gramsci, 14 - Parma, Italy Fax ++39 0524 82537 Fax ++39 0524 82537 Tel./Fax ++39 0521 033730 E-mail: [email protected] [email protected] [email protected] Index Volume 91 / Suppl. 7 June 2020 Mattioli 1885 srl - Strada di Lodesana 649/sx 43036 Fidenza (Parma) tel 0524/530383 fax 0524/82537 Original articles www.mattioli1885.com 5 Innovative therapies for malignant brain tumors: the road to a tailored cure Direttore Generale Paolo Cioni Alice Giotta Lucifero, Sabino Luzzi, Ilaria Brambilla, Chiara Trabatti, Direttore Scientifico Mario Mosconi, Salvatore Savasta, Thomas Foiadelli Federico Cioni 18 Adoptive immunotherapies in neuro-oncology: classification, recent Formazione/ECM advances, and translational challenges Simone Agnello Sabino Luzzi, Alice Giotta Lucifero, Ilaria Brambilla, Mariasole Project Manager Magistrali, Mario Mosconi, Salvatore Savasta, Thomas Foiadelli Natalie Cerioli Massimo Radaelli 32 Gene therapies for high-grade gliomas: from the bench to the bedside Editing Manager Anna Scotti Alice Giotta Lucifero, Sabino Luzzi, Ilaria Brambilla, Carmen Guarracino, Editing Mario Mosconi, Thomas Foiadelli, Salvatore Savasta Valeria Ceci Eugenio Nadotti 51 The impact of stem cells in neuro-oncology: applications, evidence, Foreign Rights limitations and challenges Nausicaa Cerioli Sabino Luzzi, Alice Giotta Lucifero, Ilaria Brambilla, Chiara Trabatti, Distribuzione Mario Mosconi, Salvatore Savasta, Thomas Foiadelli Massimiliano Franzoni 61 Potential roads for reaching the summit: an overview on target therapies for high-grade gliomas Alice Giotta Lucifero, Sabino Luzzi, Ilaria Brambilla, Lucia Schena, Mario Mosconi, Thomas Foiadelli, Salvatore Savasta EXECUtive COmmitee OF 79 Targeting the medulloblastoma: a molecular-based approach THE SOcietY OF MEDICINE Sabino Luzzi, Alice Giotta Lucifero, Ilaria Brambilla, Simona Semeria AND natUral sciences Mantelli, Mario Mosconi, Thomas Foiadelli, Salvatore Savasta OF parma President Maurizio Vanelli 101 Advanced pharmacological therapies for neurofibromatosis type Past-President 1-related tumors s Almerico Novarini Thomas Foiadelli, Matteo Naso, Amelia Licari, Alessandro Orsini, General Secretary Maria Luisa Tanzi Mariasole Magistrali, Chiara Trabatti, Sabino Luzzi, Mario Mosconi, Treasurer Salvatore Savasta, Gian Luigi Marseglia Riccardo Volpi Members O. Bussolati A. Mutti G. Ceda P. Muzzetto G. Cervellin L. Sarli G. Ceresini V. Vincenti N. Florindo V. Violi A. Melpignano M. Vitale Acta Biomed 2020; Vol. 91, Supplement 7: 5-17 DOI: 10.23750/abm.v91i7-S.9951 © Mattioli 1885 Original article Innovative therapies for malignant brain tumors: the road to a tailored cure Alice Giotta Lucifero1, Sabino Luzzi1,2, Ilaria Brambilla3, Chiara Trabatti3, Mario Mosconi4, Salvatore Savasta3, Thomas Foiadelli3 1 Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; 2 Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3 Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; 4 Orthopaedic and Traumatology Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy Abstract. Background: Immune tolerance, immune escape, neoangiogenesis, phenotypic changes, and glioma stem cells are all responsible for the resistance of malignant brain tumors to current therapies and persistent recurrence. The present study provides a panoramic view of innovative therapies for malignant brain tumors, especially glioblastoma, aimed at achieving a tailored approach. Methods: PubMed/Medline and ClinicalTri- als.gov were the main sources of an extensive literature review in which “Regenerative Medicine,” “Cell- Based Therapy,” “Chemotherapy,” “Vaccine,” “Cell Engineering,” “Immunotherapy, Active,” “Immunotherapy, Adoptive,” “Stem Cells,” “Gene Therapy,” “Target Therapy,” “Brain Cancer,” “Glioblastoma,” and “Malignant Brain Tumor” were the search terms. Only articles in English published in the last 5 years were included. A further selection was made according to the quality of the studies and level of evidence. Results: Cell-based and targeted therapies represent the newest frontiers of brain cancer treatment. Active and adoptive im- munotherapies, stem cell therapies, and gene therapies represent a tremendous evolution in recent years due to many preclinical and clinical studies. Clinical trials have validated the effectiveness of antibody-based immunotherapies, including an in-depth study of bevacizumab, in combination with standard of care. Pre- clinical data highlights the role of vaccines, stem cells, and gene therapies to prevent recurrence. Conclusion: Monoclonal antibodies strengthen the first-line therapy for high grade gliomas. Vaccines, engineered cells, stem cells, and gene and targeted therapies are good candidates for second-line treatment of both newly di- agnosed and recurrent gliomas. Further data are necessary to validate this tailored approach at the bedside. (www.actabiomedica.it) Keywords: Cell-based Therapy; Glioblastoma; Immunotherapy Malignant Brain Tumor, Target Therapy. Background median