One Treatment for Glioblastoma: Infinite Hope for Patients

Of the 23,800 brain and nervous system cancers diagnosed in American adults each year, the most common and most uniformly fatal primary brain cancer is glioblastoma (GBM). It is one of the most aggressive forms of cancer that develops from star-shaped glial cells, called astrocytes and oligodendrocytes, which support the health of the nerve cells.

A hard-to-treat cancer

The current treatment path for GBM is surgery, followed by radiation and chemotherapy (typically temozolomide). But there are challenges with this path. Not everyone responds well to treatment, while others often see their tumor become resistant or reoccur.

Sadly, despite decades of research, patients diagnosed with GBM typically survive less than 15 months after first diagnosis and only 6-9 months following relapse.

Developing treatments for GBM is especially difficult because the brain is separated from the rest of the body by the blood-brain barrier (BBB). This membrane protects the brain by preventing entry of harmful pathogens and toxins. However, the BBB also limits the ability of life-saving therapies from entering the brain.

GBM, itself, adds to the challenge.

First, the tumor is cloaked in a specialized network, known as the tumor microenvironment (TME), which supports its proliferation while concealing the tumor from the immune system.

Secondly, in and around GBM, there is a shift in the population of T helper (Th) cells, from a Th1 to Th2 bias. This shift increases the levels of growth factors like interleukin-4 (IL-4) allowing GBM and the TME to thrive because they over-express the IL-4 receptor (IL4R) which aids consumption of IL-4, unlike normal brain cells as they do not possess the IL4R.

Finally, to make things worse, GBM cells tend to infiltrate deeply into healthy brain tissue, sabotaging brain function. Therefore, treatments have to be precise and targeted to attack the tumor while avoiding harm to the healthy brain.

These features make GBM very resilient and despite decades of research no meaningful improvements in survival have manifested. At Medicenna, our approach to GBM is unconventional. but very tactical by leveraging the knowledge we have about the enemy within.

Attacking GBM with A Molecular Trojan Horse (MDNA55)

Knowing that GBM and the TME consume IL-4, our drug, MDNA55 was designed as a Molecular Trojan Horse. We engineered IL-4 so that it binds with high affinity to the IL4R. We then fused a potent toxin to our IL-4 creating MDNA55, an IL-4 Empowered Superkine. Tumor cells and TME consume MDNA55 as though it is a nutrient but the toxic payload kills the target – a clever trick.

By-passing the BBB and uncloaking GBM with MDNA55

To get past the natural barriers, Medicenna delivers the drug directly into and around the tumor using a highly precise technique known as convection enhanced delivery. For neurosurgeons, it is an adaptation of a routine brain tumor biopsy procedure. A proprietary catheter is accurately placed inside the tumor and our drug MDNA55 is infused in and around the tumor and the TME. After approximately one day, the catheter is removed and the patient discharged without any further treatment with MDNA55.

Care and to Cure

Clinical data to date with MDNA55, are compelling. By delivering MDNA55 directly into the tumor, we can avoid systemic toxicity associated with conventional therapies. Results with MDNA55 show a doubling of survival of recurrent GBM patients from 6-9 months to 15 months following only one treatment. The potential for further improving survival outcomes with repeat MDNA55 treatments or combinations with other therapies are yet to be explored but the promise for better outcomes may be on the horizon for this terrible disease.