Genetically-engineered olfactory cells successfully bypass the BBB to kill brain cancer tumours.


Olfactory neurons are cells in the nasal cavity which perceive odors, passing the information along to the brain, and have the ability to regenerate.  They project axons to the olfactory bulb within the brain itself with olfactory ensheathing cells surrounding the growing axons, assisting in their regeneration. The ability of olfactory ensheathing cells to promote neural regeneration has led to studies of their potential in the treatment of spinal cord injuries as well as amyotrophic lateral sclerosis, however, there have never been studies in the discipline of cancer.  Now, a study from researchers at  Massachusetts General Hospital genetically engineers olfactory ensheathing cells to deliver anticancer therapy to dangerous brain tumours called glioblastomas.  The team state their olfactory ensheathing cells bypassed the blood-brain barrier to deliver an anticancer agent only to the tumour cells, and reduced tumour size to prolong survival in a mouse model.  The study is published in the Journal of the National Cancer Institute.

Previous studies show that glioblastomas are the most aggressive form of brain tumours which usually recur, leading to a five-year survival rate of less than 10%.  It is known that olfactory ensheathing cells migrate from the peripheral nervous system to the central nervous system, a critical process for the development of the olfactory system and axonal extension after injury in neural regeneration.  Due to their ability to migrate to the injury site and anti-inflammatory properties, they have been investigated in many different neurologic pathologies.  The current study investigates olfactory ensheathing cells’ ability to target gliomas, traverse the blood-brain barrier and to deliver anti-cancer agents through the nasal pathway to the central nervous system.

The current study genetically engineers olfactory ensheathing cells to express a fusion protein called CU which converts a nontoxic drug called 5-FC into a cell-killing chemotherapy agent called 5-FU.  The group administered either CU-expressing olfactory ensheathing cells or a control agent into the nasal cavities of mice with glioblastoma.  Results show mice that had received the transgenic olfactory ensheathing cells had significantly smaller tumours at the injection site, less tumour migration through the brain and greater death of tumour cells than the control group. Data findings show that the single olfactory ensheathing cell treatment also led to significantly longer survival.

The team explain their findings indicate that, upon intranasal delivery, CU-expressing olfactory ensheathing cells migrate through their natural route towards the brain.  Data findings show that upon arrival the olfactory ensheathing cells target brain tumours in a very specific manner and convert 5-FC into an active 5-FU drug at the tumour site, leading to an efficient, tumour-cell-killing effect through what is called a ‘bystander effect’.

The team surmise they have shown that olfactory ensheathing cells can target and deliver therapeutic transgenes to brain tumours upon intranasal delivery to the central nervous system.  For the future, the researchers state that olfactory ensheathing cells could be used as a therapeutic tool against different types of brain cancer and tumours located in other parts of the body.

Source: Massachusetts General Hospital

 

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