Background/problem
Glioblastoma (GBM) is the most common malignant, primary brain tumor observed in adults, occurring at an incidence rate of 3.19 per 100,000 persons in the United States in 2017. Even with complete surgical resection of the tumor and adjuvant chemotherapy, these tumors often reoccur, resulting in a median survival of ~15 months. Part of the poor prognosis is that many therapeutics cannot cross the blood-brain barrier, and those that do result in poor efficacy due to inefficient accumulation in glioblastoma cells. Oncolytics is an advanced biological therapy that uses microorganisms as “drug delivery systems” to treat cancer. Microorganisms have unique benefits, including dose independence, ability to produce therapeutic proteins locally within the tumor, and simplicity of administration. However, current microbial delivery systems (e.g., AAV9 and herpes virus) have limited instruction capacity, minimal cancer cell selectivity, and poor innate cytotoxicity.
Tech overview/solution
To address these issues, researchers at The University of Texas at Austin developed a bacterial-based drug delivery system, based on S. flexneri, that selectively internalizes into GBM cells. This novel GBM-treatment platform is based on a non-toxin-containing Shigella strain. In addition, it has a type-3 secretion system capable of encoding therapeutic proteins into the GBM cytosol by virtue of its unlimited “cassette space.” Through a patent-pending process, the GBM-engineered S. flexneri was able to selectively internalize within 95% GBM cells in two hours, with a 124-fold preference (in nine different GBM cell lines) vs. controls.
Benefits
Microorganism-based drug delivery systems are emerging as a promising approach to treat solid tumors, with the potential to radically improve outcomes compared to traditional chemotherapy. The bioengineered microorganisms can deliver the therapeutics continuously after only one dose until the therapy is turned off. This specific technology can encode various therapeutic proteins into the GBM cytosol while being amenable to further engineering towards biosafety.
Opportunity
- The use of an oncolytic approach to target GBM was part of the National Cancer Moonshot program in the United States.
- The global adult malignant glioma therapeutics market size stood at $1.5B in 2018, $2.9B in 2024, and is projected to reach $5.4B by the end of 2032, exhibiting a CAGR of 9.8%.
- For parties/companies with interest in therapeutics, drug delivery, neurology, GBM, brain tumors
