Welcome to IOTA's blog: Window on Glioblastoma


CAR-T Cell Therapies in Glioblastoma: tumour editing shows promise in the clinic

Download this article as a pdf here.
SPACE
Executive summary
The immune system surveys the body throughout a person’s life to detect and eliminate tumour cells as well as infections such as influenza. In cancer patients, tumour cells have escaped these body defences and grow unchecked. Scientists and clinicians now have the tools to create new defences, in the form of CAR T-cells, which are manufactured from the patient’s own white blood cells using genetic engineering. This article describes the results of preliminary clinical trials using specially designed CAR-T-cells in glioblastoma patients. The results provide a starting point from which potentially curative therapies can be developed.
SPACE
Background
The recent application of immunotherapies to control or even cure some cancers has been hailed as a ‘game changer’ in the field of cancer therapy and has prompted an explosion of related activity in academia and industry. It is perhaps not too fanciful to predict the eventual elimination of at least some cancers as chronic diseases1. Several different strategies are being employed, including vaccination with tumour antigens2, checkpoint inhibition with antibodies to cell surface molecules expressed on tumours3 and adoptive immunotherapy with patient-derived cytotoxic T lymphocytes4. While each approach has potential utility in treating glioblastomas (which will be highlighted in future Window on Glioblastoma articles), here we review some of the first clinical studies in this disease using adoptive immunotherapy with CAR T-cells.
Continue reading

Posted in Uncategorized | Leave a comment

Targeting Neuroligin-3 Secretion in Glioblastoma: impact of the tumour microenvironment

Download this article as a pdf here.
SPACE
Executive summary
Tumours do not grow in isolation, but are supported by normal cells in the body, sometimes called the ‘tumour microenvironment’. The findings highlighted in this article describe a mouse model in which the brain microenvironment (neurons and astrocytes) can artificially stimulate the growth of implanted human glioblastoma cells. A specific protein, neuroligin-3 (NLGN3) was shown to be responsible for this growth, and the investigators identified a way in which its production can be stopped using a small molecule drug. Although there are technical reasons why this specific type of drug may not be clinically useful, the target NLGN3 itself is of great interest and may offer an effective way to treat glioblastoma and other brain cancers in the future.
SPACE
Background
Most attention in cancer research has understandably been focussed on the transformed cells that form the tumour mass and subsequent metastases. However, it is also appreciated that the tumour microenvironment is of critical importance in supporting tumour growth through crosstalk via signalling molecules.1 Aggressive brain cancers, such as glioblastoma (GBM), are no exception to this, as highlighted by work showing how neuronal activity stimulates the growth of two cell types thought to give rise to glioma, namely oligodendroglial precursor cells and earlier neural precursor cells.2 A subsequent paper by Venkatesh et al in 2015 (3 and commentaries in 4,5) took this one step further and identified the synaptic adhesion molecule neuroligin-3 (NLGN3) as a direct stimulator of glioma proliferation through the PI3K–mTOR signalling pathway. This Window on Glioblastoma article focusses on a subsequent (2017) paper by the same group in which they inhibit the secretion of NLGN3 from neuronal cells thereby preventing glioma cell growth in vivo.6 This inhibition was achieved using inhibitors of the ADAM10 sheddase enzyme, both of which are in clinical development for other cancers and therefore may also be of use in GBM treatment.
Continue reading

Posted in Uncategorized | Leave a comment