This innovative treatment causes cancer cells to self-destruct: Here's how
What's the story
Scientists from the University of Pennsylvania have developed an innovative cancer treatment using small extracellular vesicles (sEVs).
These tiny capsules, as reported in Science Advances, target a specific receptor on tumor cells known as DR5 (death receptor 5).
This receptor plays a key role in cancer treatment. It's activation can trigger apoptosis, leading to the self-destruction of cancerous cells.
This new approach has shown significant effectiveness against various types of cancer in preclinical studies.
Superior performance
Outperforming traditional DR5-targeting antibodies
The use of sEVs in targeting the DR5 receptor has been found to be more effective than previous methods, including those involving DR5-targeting antibodies.
The antibodies have long been considered the gold standard in cancer treatment.
Dr. Xiaowei "George" Xu, a professor at Penn Pathology and Laboratory Medicine, expressed enthusiasm about this new strategy saying, "Our preclinical results are promising, and we're eager to take this step forward into human clinical trials."
Scenario
Boosting DR5 treatment efficacy
The DR5 receptor is particularly fascinating as it seems to have evolved to target and eliminate damaged or malignant cells.
However, despite its potential, current DR5-targeting treatments have faced challenges in halting tumor progression.
To improve the effectiveness of these therapies, Dr. Xu and his team turned to sEVs—tiny capsules produced by all cells that carry crucial signals to nearby tissues.
Strategic enhancement
sEVs derived from natural killer cells
For this study, Dr. Xu's team employed sEVs from natural killer (NK) cells. These immune cells are famous for their cancer-fighting properties.
The researchers engineered these sEVs to carry an antibody fragment capable of activating the DR5 receptor, enabling them to efficiently target and kill cancer cells with high DR5 expression.
This includes those linked to melanoma, liver, and ovarian cancers.
Significant reductions
Engineered sEVs show remarkable ability in lab tests
In lab tests, the engineered sEVs showed an incredible ability to home in on DR5-positive cancer cells, drastically reducing tumor size.
In mouse models of melanoma, breast, and liver cancers, the sEVs suppressed tumor growth and prolonged the animals' survival compared to those treated with conventional DR5-targeting antibodies.
The team also discovered the sEVs could attack cancer-associated fibroblasts and myeloid-derived suppressor cells, both of which create an immune-suppressive environment for tumors to grow.
Immune stimulation
sEVs stimulate T cells, enhancing immune response against cancer
Apart from directly attacking the cancer cells, the sEVs also activate T cells, thus boosting the immune response against cancer.
This distinctive capability to break the immunosuppressive tumor micro-environment makes sEVs a promising candidate for the effective treatment of solid tumors.
One of the major benefits of this method is the ease of manufacturing and storing sEVs, which could potentially enable an "off-the-shelf" therapy.
Upcoming trials
Future plans for clinical-grade sEVs and human trials
Looking ahead, Dr. Xu and his team intend to refine the production process to create clinical-grade sEVs and conduct safety studies in preparation for future human trials.
Funded by the National Institutes of Health, this research promises to revolutionize cancer treatment and offer new hope to patients facing aggressive forms of the disease.