Nanomedicine and Immunotherapy for recurrent glioblastoma

4 min read

Research:  

Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment. Gboxin suppresses the growth of glioblastoma (GBM) cells by inhibiting a stage of respiration (oxidative phosphorylation) that occurs in mitochondria. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites.  This study, published in Nature Communications, presents a delivery system that helps transport Gboxin to the target mitochondria using a membrane containing both cancer cell and mitochondrial membrane features. Using this delivery method, the researchers achieved potent GBM tumour inhibition in vitro and in vivo leading to prolonged median survival time in mouse models. 

Immunohistochemical Analysis of PD-1 and FOXP3 in Tumour-Infiltrating Lymphocytes in Human Gliomas. In this study, researchers investigated the expression profiles of PD-1 and FOXP3 in tumour infiltrating lymphocytes (an immune cell) of astrocytic and oligodendroglial lineages of gliomas.  

The researchers stated that their work implied that “PD-1 and FOXP3 expressions in glioma infiltrating lymphocytes play a significant role in the progression of the tumour into high-grade neoplasm and may be linked to the biological malignancy of high-grade glial tumours”. The findings, published in Cureus,  also point to the possibility of immune checkpoint inhibitors being useful. With more research and investigations, it is possible that both PD-1 and FOXP3 will emerge as novel glioma molecular markers and therapeutic targets. 

EYA2 Tyrosine Phosphatase Inhibition Reduces MYC and Prevents Medulloblastoma Progression. In this study, patient gene expression data was used to identify high levels of EYA2 (which has been shown to be dysregulated in various tumours) in Group 3 medulloblastoma (MB) samples, assess the correlation between EYA2 and MYC (a family of proteins involved in cancer development), and examine patient survival.  The paper, published in Neuro-Oncology, showed that EYA2 is more highly expressed in Group 3 MB than other MB subtypes and is essential for Group 3 MB growth in vitro and in vivo.  They concluded that “EYA2 is a critical regulator of MYC in Group 3 MB and suggest a novel therapeutic avenue to target this highly lethal disease.”  

Treatments:  

Immune Changes Show Response Correlation with VT1021 in Recurrent GBM. According to results presented at the 2023 ASCO Annual Meeting, the use of the novel therapeutic VT1021 in patients with recurrent glioblastoma (rGBM) showed durable responses by inhibiting the tumour growth via stimulation of thrombospondin-1, which altered the tumour microenvironment. They also reported that long-term findings showed that patients with a better immune response throughout treatment had better results compared with those who did not exhibit much of an immune response. This article includes an interview with Dr Peereboom who presented the findings at ASCO, who goes on to explain more about the results.  

Reviews:  

Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults  This literature review summarises the recent clinical studies of immunotherapy for recurrent glioblastoma, including that of immune checkpoint blockade, oncolytic virotherapy, chimeric antigen receptor (CAR) T-cell therapy, cancer vaccine and antibody-conjugated toxin. Published in Cancers, it provides an overview of treatment advances, limitations in each strategy, ongoing opportunities, and preliminary correlates to survival, in order to support clinical decision-making and guide future research endeavours. 

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