Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma
| Autor: | Kirit Singh, David A. Reardon, John Sampson, Rifaquat Rahman, Stephen J Bagley, Solmaz Sahebjam, Amy B. Heimberger, Alireza Mansouri, Donald A. Berry, John Simes, David M. Ashley, Evanthia Galanis, Michael Weller, Howard Colman, Michael Lim, Timothy F. Cloughesy, Gelareh Zadeh, Steven Piantadosi, Vinay K. Puduvalli, Minesh P. Mehta, Aaron Tan, Michael Platten, Patrick Y. Wen, Susan M. Chang, Kristen A. Batich, Mustafa Khasraw |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Systemic immunosuppression medicine.medical_treatment Clinical Trials and Supportive Activities Oncology and Carcinogenesis Clinical settings Bioinformatics Vaccine Related T-cell dysfunction Rare Diseases Clinical Research medicine Immune Tolerance Humans Oncology & Carcinogenesis Combination immunotherapy Cancer Immunosuppression Therapy business.industry Brain Neoplasms Immunotherapy medicine.disease Brain Disorders 8.4 Research design and methodologies (health services) Brain Cancer Clinical trial Oncology 5.1 Pharmaceuticals Immunization Development of treatments and therapeutic interventions business Glioblastoma Health and social care services research |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research, vol 28, iss 4 |
| ISSN: | 1557-3265 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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