TY - JOUR
T1 - Prospects of immune checkpoint modulators in the treatment of glioblastoma
AU - Preusser, Matthias
AU - Lim, Michael
AU - Hafler, David A.
AU - Reardon, David A.
AU - Sampson, John H.
N1 - Funding Information:
M.P. has received honoraria, research support (unrestricted grants), and travel support (to scientific meetings) from Bristol-Myers Squibb, Böhringer-Ingelheim, GlaxoSmithKline, Mundipharma and Roche. M.L. has received research support from Agenus, Arbor Pharmaceuticals, Bristol-Myers Squibb, Celldex Therapeutics, and ImmunoCellular Therapeutics, and has served as a consultant for Bristol-Myers Squibb. D.A.H. has consulted for Allergan Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Genzyme Sanofi-Aventis, MedImmune, Mylan Pharmaceuticals, Novartis Pharmaceuticals, Questcor and Teva Neuroscience, and has received grant support from Bristol-Myers Squibb. D.A.R. has received financial compensation for participation in advisory boards for Amgen, Cavion, Genentech/ Roche, Midatech Pharma, Momenta Pharmaceuticals, Novartis and Stemline Therapeutics, served as a member of speakers’ bureaus for Genentech/Roche and Merck, and received research support from Celldex Therapeutics and Incyte. J.H.S. declares no competing interests.
Funding Information:
M. Daniels from inScience Communications in Philadelphia, PA, USA, provided editorial support for writing this article, comprising compilation of tables, management of the reference database, and editing of the manuscript text before submission. The editorial support was funded by Bristol-Myers Squibb. D.A.H. has received the National Multiple Sclerosis Society Collaborative Research Centre Award CA1061-A-18, NIH grants P01 AI045757, U19 AI046130, U19 AI070352, and P01 AI039671, and research support from the Nancy Taylor Foundation for Chronic Diseases and the Penates Foundation. J.H.S. has received the NIH grants R01-CA177476-02, R01-NS086943-01, P50-CA190991-01, and 2R25-NS065731-06, and research support from the Accelerate Brain Cancer Cure and Pediatric Brain Tumor Foundation.
Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/9/7
Y1 - 2015/9/7
N2 - Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment - maximal safe resection and combination of radiotherapy with temozolomide chemotherapy - the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies.
AB - Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment - maximal safe resection and combination of radiotherapy with temozolomide chemotherapy - the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies.
UR - http://www.scopus.com/inward/record.url?scp=84941025149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941025149&partnerID=8YFLogxK
U2 - 10.1038/nrneurol.2015.139
DO - 10.1038/nrneurol.2015.139
M3 - Review article
C2 - 26260659
AN - SCOPUS:84941025149
VL - 11
SP - 504
EP - 514
JO - Nature Clinical Practice Neurology
JF - Nature Clinical Practice Neurology
SN - 1759-4758
IS - 9
ER -