Abstract
Immunotherapeutics have revolutionized the management of solid malignancies over the last few years. Nevertheless, despite relative successes of checkpoint inhibitors in numerous solid tumour types, success in tumours of the central nervous system (CNS) has been lacking. There are several possible reasons for the relative lack of success of immunotherapeutics in this setting, including the immune microenvironment of glioblastoma, lymphocyte tracking through the blood-brain barrier (BBB) into the central nervous system and impairment of drug delivery into the CNS through the BBB. This review utilizes the cancer-immunity cycle as a conceptual framework through which the specific challenges associated with the development of immunotherapeutics for CNS malignancies can be viewed.
Highlights
The recent development of immune checkpoint inhibitors and the corresponding efficacy shown by inhibitors of the CTLA-4/B7 [1] and PD-1/PD-L1 checkpoints [2,3,4,5,6,7] in multiple tumour types has resulted in substantial investment by the pharmaceutical industry in clinical development of immunotherapeutics across tumour types and indications
The efficacy of inhibitors of the PD-1/PD-L1 checkpoint has been consistent across tumour types, the single agent activity of these drugs has been lacking in tumours of the central nervous system (CNS)
This review evaluates the challenges of developing successful immunotherapeutics for glioblastoma through the lens of the cancer-immunity cycle
Summary
The recent development of immune checkpoint inhibitors and the corresponding efficacy shown by inhibitors of the CTLA-4/B7 [1] and PD-1/PD-L1 checkpoints [2,3,4,5,6,7] in multiple tumour types has resulted in substantial investment by the pharmaceutical industry in clinical development of immunotherapeutics across tumour types and indications. This review utilizes the cancer-immunity cycle as a conceptual framework through which the specific challenges associated with the development of immunotherapeutics for CNS malignancies can be viewed.
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