Abstract
Progress in the treatment of glioblastoma multiforme (GBM) over the last few decades has remained marginal and GBM is still universally fatal with short survival times after initial diagnosis. Much research is focused on finding new therapeutics for GBM and immune-based approaches have shown great promise. The detection of cytomegalovirus (CMV) antigens in malignant cells has suggested that treatment strategies based on immunological intervention, such as adoptive transfer of antiviral T cells or vaccination with viral epitopes, could be exploited as cancer therapy. Here, we review the rationale for using CMV as a therapeutic target and discuss the first clinical evidence for safety and efficacy of CMV-specific cellular immunotherapy for GBM.
Highlights
Temozolomide was the last drug to bring a significant improvement of survival for patients with glioblastoma multiforme (GBM) brain cancer [1]
Most cellular immunotherapies for GBM under investigation at the moment focus on using tumor lysate loaded dendritic cells (DCs) or vaccination using tumor peptides [for an overview see recent review in Ref. [4]]
Immunotherapies provide a novel approach to complement standard therapies for GBM treatment (Figure 1)
Summary
Temozolomide was the last drug to bring a significant improvement of survival for patients with glioblastoma multiforme (GBM) brain cancer [1]. This suggests that adoptive transfer of in vitro expanded T cells could improve CMV-specific immune responses in GBM patients This preliminary study has shown that immunotherapy using CMV-specific T cells was coincident with prolonged survival in one patient [32]. Molecular analysis of the T cell product used for adoptive therapy showed a signature of seven genes (EOMES, IFNG, BCL6, XAF1, CCL5, CTLA-4, FOXP3) that distinguished individuals with long-term progression free survival from patients that progressed more rapidly This signature was consistent with T cell activation (i.e., upregulation of T cell transcription factor Eomes and effector molecule IFNγ, downregulation of inhibitory receptor CTLA-4) suggesting that more functional CMV-specific T cells are more efficient in controlling cancer relapse. One patient had a tumor recurrence after therapy and isolation of T cells
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