Suicide gene therapy, cancer-targeting viruses and radiation

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Research

Radiation combined with cancer-targeting virus therapy is more effective in fighting brain tumours According to research from the University of Alberta, combining a cancer-targeting virus with radiation to treat brain cancer in mice was more effective than either therapy on its own. The researchers treated mice with glioblastoma brain tumours simultaneously with high-dose radiation and a genetically engineered oncolytic vaccinia virus, a virus that has been used safely as a vaccine against smallpox. The study showed that 67% of the mice treated with both therapies were cleared of their tumours.

Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma Chitinase 3-like 1 (Chi3l1) is a secreted protein that is highly expressed in glioblastoma. This study, published in Cancer Research, shows that Chi3l1 alters the state of glioma stem cells (GSC) to support tumour growth. The researchers concluded that Chi3l1 could be a targetable vulnerability which may promote differentiation and suppress growth of glioblastoma.

New and significant breakthrough made to detect brain tumors Researchers have discovered that brain tumours have an increased amount of folate receptor expression relative to adjacent brain tissue. The researchers suggested that this increased expression could be exploited by using folate-based radiopharmaceuticals in position emission tomography (PET) imaging to detect folate receptors in the brain, helping differentiate between tumour and healthy tissue. This study, published in Frontiers in Immunology, demonstrated an average 100-fold increase in folate-based radiopharmaceutical accumulation in glioma tissue versus that of healthy brain tissue.

The overexpression and clinical significance of TBX15 in human gliomas This study, published in Scientific Reports, found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 is a transcription factor that is known to regulate a variety of developmental processes. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. The researchers concluded that TBX15 plays an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.

Treatments

Bavituximab decreases immunosuppressive myeloid-derived suppressor cells in newly diagnosed glioblastoma patients The purpose of this study was to evaluate the efficacy of bavituximab – a monoclonal antibody with anti-angiogenic and immunomodulatory properties – in newly diagnosed glioblastoma patients who also received radiation and temozolomide. Published in Clinical Cancer Research, it demonstrated that bavituximab has activity in newly diagnosed glioblastoma patients and resulted in on-target depletion of intratumoural immunosuppressive myeloid-derived suppressor cells (a type of immune cell). In addition, elevated expression of myeloid-related transcripts in glioblastoma before treatment may predict response to bavituximab.

Suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cell gene delivery vehicles in recurrent glioblastoma multiforme: a first-in-human, dose-escalation, phase I clinical trial This phase 1 clinical trial, published in Journal of Translational Medicine, has demonstrated that suicide gene therapy using allogeneic adipose tissue-derived stem cells carrying the HSV-TK gene is safe in patients with recurrent glioblastoma. Researchers concluded that future phase II/III clinical trials with multiple arms are warranted to validate the findings and further investigate the efficacy of this protocol compared with standard therapy alone. 

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