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

Olfactory neurons are cells in the nasal cavity with the ability to regenerate, responsible for perceiving odors and passing the information along to the brain.  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, research is lacking with regards to the effects of this mechanism on cancer.  Now, a study from researchers at  Massachusetts General Hospital genetically engineers olfactory ensheathing cells to deliver anticancer therapy to dangerous brain tumors called glioblastomas.  The team states their olfactory ensheathing cells bypassed the blood-brain barrier to deliver an anticancer agent only to the tumor cells and reduced tumor size to prolong survival in a mouse model.  The study is published in the Journal of the National Cancer Institute.

Previous studies show glioblastomas are the most aggressive form of brain tumors leading to a five-year survival rate of less than 10%, they are also known to recur.  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 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 that 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 the mouse model of glioblastoma.  Results show mice that received the transgenic olfactory ensheathing cells had significantly smaller tumors at the injection site, less tumor migration through the brain and greater death of tumor cells than the control group. Data findings show the single olfactory ensheathing cell treatment also led to significantly longer survival.

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

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

Source: Massachusetts General Hospital

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