Michael Zhang1, John Choi1, Michael Lim2,3. 1. Department of Neurosurgery, Stanford University, Stanford, CA, 94305, USA. 2. Department of Neurosurgery, Stanford University, Stanford, CA, 94305, USA. mklim@stanford.edu. 3. Department of Neurosurgery, Departments of Oncology, Otolaryngology, and Radiation Oncology, 453 Quarry Road, Neurosurgery 5327, Palo Alto, CA, 94304, USA. mklim@stanford.edu.
Abstract
PURPOSE OF REVIEW: Immunotherapy-based treatment of glioblastoma has been challenging because of the tumor's limited neoantigen profile and weakly immunogenic composition. This article summarizes the current clinical trials underway by evaluating the leading immunotherapy paradigms, the encountered barriers, and the future directions needed to overcome such tumor evasion. RECENT FINDINGS: A limited number of phase III trials have been completed for checkpoint inhibitor, vaccine, as well as gene therapies, and have been unable to show improvement in survival outcomes. Nevertheless, these trials have also shown these strategies to be safe and promising with further adaptations. Further large-scale studies for chimeric antigen receptors T cell therapies and viral therapies are anticipated. Many current trials are broadening the number of antigens targeted and modulating the microtumor environment to abrogate early mechanisms of resistance. Future GBM treatment will also likely require synergistic effects by combination regimens.
PURPOSE OF REVIEW: Immunotherapy-based treatment of glioblastoma has been challenging because of the tumor's limited neoantigen profile and weakly immunogenic composition. This article summarizes the current clinical trials underway by evaluating the leading immunotherapy paradigms, the encountered barriers, and the future directions needed to overcome such tumor evasion. RECENT FINDINGS: A limited number of phase III trials have been completed for checkpoint inhibitor, vaccine, as well as gene therapies, and have been unable to show improvement in survival outcomes. Nevertheless, these trials have also shown these strategies to be safe and promising with further adaptations. Further large-scale studies for chimeric antigen receptors T cell therapies and viral therapies are anticipated. Many current trials are broadening the number of antigens targeted and modulating the microtumor environment to abrogate early mechanisms of resistance. Future GBM treatment will also likely require synergistic effects by combination regimens.
Authors: Giulia Escobar; Davide Moi; Anna Ranghetti; Pinar Ozkal-Baydin; Mario Leonardo Squadrito; Anna Kajaste-Rudnitski; Attilio Bondanza; Bernhard Gentner; Michele De Palma; Roberta Mazzieri; Luigi Naldini Journal: Sci Transl Med Date: 2014-01-01 Impact factor: 17.956
Authors: Donald M O'Rourke; MacLean P Nasrallah; Arati Desai; Jan J Melenhorst; Keith Mansfield; Jennifer J D Morrissette; Maria Martinez-Lage; Steven Brem; Eileen Maloney; Angela Shen; Randi Isaacs; Suyash Mohan; Gabriela Plesa; Simon F Lacey; Jean-Marc Navenot; Zhaohui Zheng; Bruce L Levine; Hideho Okada; Carl H June; Jennifer L Brogdon; Marcela V Maus Journal: Sci Transl Med Date: 2017-07-19 Impact factor: 17.956
Authors: Daxa M Patel; Paul M Foreman; L Burt Nabors; Kristen O Riley; G Yancey Gillespie; James M Markert Journal: Hum Gene Ther Clin Dev Date: 2016-06 Impact factor: 5.032
Authors: Erik Ladomersky; Lijie Zhai; Alicia Lenzen; Kristen L Lauing; Jun Qian; Denise M Scholtens; Galina Gritsina; Xuebing Sun; Ye Liu; Fenglong Yu; Wenfeng Gong; Yong Liu; Beibei Jiang; Tristin Tang; Ricky Patel; Leonidas C Platanias; C David James; Roger Stupp; Rimas V Lukas; David C Binder; Derek A Wainwright Journal: Clin Cancer Res Date: 2018-03-02 Impact factor: 12.531