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Designing clinical trials for combination immunotherapy: a framework for glioblastoma

Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engender...

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Main Authors: Singh, Kirit (Author) , Batich, Kristen A. (Author) , Wen, Patrick Y. (Author) , Tan, Aaron C. (Author) , Bagley, Stephen J. (Author) , Lim, Michael (Author) , Platten, Michael (Author) , Colman, Howard (Author) , Ashley, David M. (Author) , Chang, Susan M. (Author) , Rahman, Rifaquat (Author) , Galanis, Evanthia (Author) , Mansouri, Alireza (Author) , Puduvalli, Vinay K. (Author) , Reardon, David A. (Author) , Sahebjam, Solmaz (Author) , Sampson, John H. (Author) , Simes, John (Author) , Berry, Donald A. (Author) , Zadeh, Gelareh (Author) , Cloughesy, Tim F. (Author) , Mehta, Minesh P. (Author) , Piantadosi, Steven (Author) , Weller, Michael (Author) , Heimberger, Amy B. (Author) , Khasraw, Mustafa (Author)
Format: Article (Journal)
Language:English
Published: 15 February 2022
In: Clinical cancer research
Year: 2022, Volume: 28, Issue: 4, Pages: 585-593
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-21-2681
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-21-2681
Verlag, lizenzpflichtig, Volltext: https://aacrjournals.org/clincancerres/article/28/4/585/678113/Designing-Clinical-Trials-for-Combination
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Author Notes:Kirit Singh, Kristen A. Batich, Patrick Y. Wen, Aaron C. Tan, Stephen J. Bagley, Michael Lim, Michael Platten, Howard Colman, David M. Ashley, Susan M. Chang, Rifaquat Rahman, Evanthia Galanis, Alireza Mansouri, Vinay K. Puduvalli, David A. Reardon, Solmaz Sahebjam, John H. Sampson, John Simes, Donald A. Berry, Gelareh Zadeh, Tim F. Cloughesy, Minesh P. Mehta, Steven Piantadosi, Michael Weller, Amy B. Heimberger, and Mustafa Khasraw
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Summary:Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents.
Item Description:Gesehen am 27.05.2024
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-21-2681

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