TY - JOUR
T1 - Recent developments on immunotherapy for brain cancer
AU - Wainwright, Derek A.
AU - Nigam, Pragati
AU - Thaci, Bart
AU - Dey, Mahua
AU - Lesniak, MacIej S.
N1 - Funding Information:
This work was supported by the NIH grants R01 CA138587, NIH R01 CA122930, NIH U01 NS069997 and ACS RSG-07-276-01 to MS Lesniak. It was also supported by the NIH grant F32 NS073366 to DA Wainwright. The authors declare no other conflicts of interest.
PY - 2012/6
Y1 - 2012/6
N2 - Introduction: Brain tumors are a unique class of cancers since they are anatomically shielded from normal immunosurveillance by the bloodbrain barrier, lack a normal lymphatic drainage system and reside in a potently immunosuppressive environment. Of the primary brain cancers, glioblastoma multiforme (GBM) is the most common and aggressive in adults. Although treatment options include surgery, radiation and chemotherapy, the average lifespan of GBM patients remains at only 14.6 months post-diagnosis. Areas covered: A review of key cellular and molecular immune system mediators in the context of brain tumors including TGF-β, cytotoxic T cells, Tregs, CTLA-4, PD-1 and IDO is discussed. In addition, prognostic factors, currently utilized immunotherapeutic strategies, ongoing clinical trials and a discussion of new or potential immunotherapies for brain tumor patients are considered. Expert opinion: Current drugs that improve the quality of life and overall survival in patients with brain tumors, especially for GBM, are poorly effective. This disease requires a reanalysis of currently accepted treatment strategies, as well as newly designed approaches. Here, we review the fundamental aspects of immunosuppression in brain tumors, new and promising immunotherapeutic drugs as well as combinatorial strategies that focus on the simultaneous inhibition of immunosuppressive hubs, both in immune and brain tumor cells, which is critical to consider for achieving future success for the treatment of this devastating disease.
AB - Introduction: Brain tumors are a unique class of cancers since they are anatomically shielded from normal immunosurveillance by the bloodbrain barrier, lack a normal lymphatic drainage system and reside in a potently immunosuppressive environment. Of the primary brain cancers, glioblastoma multiforme (GBM) is the most common and aggressive in adults. Although treatment options include surgery, radiation and chemotherapy, the average lifespan of GBM patients remains at only 14.6 months post-diagnosis. Areas covered: A review of key cellular and molecular immune system mediators in the context of brain tumors including TGF-β, cytotoxic T cells, Tregs, CTLA-4, PD-1 and IDO is discussed. In addition, prognostic factors, currently utilized immunotherapeutic strategies, ongoing clinical trials and a discussion of new or potential immunotherapies for brain tumor patients are considered. Expert opinion: Current drugs that improve the quality of life and overall survival in patients with brain tumors, especially for GBM, are poorly effective. This disease requires a reanalysis of currently accepted treatment strategies, as well as newly designed approaches. Here, we review the fundamental aspects of immunosuppression in brain tumors, new and promising immunotherapeutic drugs as well as combinatorial strategies that focus on the simultaneous inhibition of immunosuppressive hubs, both in immune and brain tumor cells, which is critical to consider for achieving future success for the treatment of this devastating disease.
KW - CTLA-4
KW - Glioblastoma
KW - Glioma
KW - IDO
KW - PD-1
KW - Rindopepimut
KW - TGF-β
KW - Treg
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U2 - 10.1517/14728214.2012.679929
DO - 10.1517/14728214.2012.679929
M3 - Review article
C2 - 22533851
AN - SCOPUS:84861589683
VL - 17
SP - 181
EP - 202
JO - Expert Opinion on Emerging Drugs
JF - Expert Opinion on Emerging Drugs
SN - 1472-8214
IS - 2
ER -