Nanotechnology

Tiny anti-cancer weapons: nano-sized particles cause tumor cells to self-destruct

DR5-scFv induces apoptosis of DR5+ tumor cells. Credit: Science Advances (2025). DOI: 10.1126/sciadv.adp9009

A preclinical study by researchers at the Perelman School of Medicine at the University of Pennsylvania has added a new twist to a decades-old anti-cancer strategy, showing powerful effects against multiple cancer types. This experimental approach, which uses tiny capsules called small extracellular vesicles (sEVs), has the potential to provide an innovative new type of immunotherapy treatment and is poised to move toward more advanced development and testing. It’s done.

The study is published in the journal Science Advances.

The researchers described how they used sEVs made from human cells in the lab to target a cell surface receptor called DR5 (death receptor 5), which many tumor cells have. are. Once activated, DR5 can cause the death of these cells through a self-destructive process called apoptosis.

Researchers have been working for more than 20 years to successfully develop cancer treatments that target DR5. A new approach using engineered sEVs to target DR5 has outperformed DR5-targeting antibodies, which are considered the primary DR5-targeting strategy. sEV effectively killed multiple cancer cell types in lab dish tests, blocked tumor growth in mouse models, and enabled much longer survival than antibodies targeting DR5.

“This new strategy has many advantages compared to previous DR5-targeted strategies and other anti-cancer immunotherapies, and these promising preclinical results encourage us to further develop it for human clinical trials. said lead author Xiaowei “George” Xu, MD. , PhD, is a professor of pathology and laboratory medicine and a member of the Tara Miller Melanoma Center at Abramson Cancer Center in Medicine, Pennsylvania.

“While we have seen many patients benefit from advances in cancer immunotherapy, we know there is still much work to be done. We are motivated to explore new strategies for cell therapy in solid tumor cancers such as melanoma, where efficacy is true for approximately half of patients. ”

A better way to target DR5

The DR5 death receptor appears to have evolved, at least in part, to destroy malignant and damaged cells. DR5 appears to be an attractive target for cancer therapy, but those developed so far have not been successful in controlling tumor growth. Xu and his team used extracellular vesicles to target DR5. That’s because these nanosized capsules (about one millionth the size of a T cell) are naturally produced and secreted by virtually all cells. Extracellular vesicles carry molecules that can convey messages to surrounding cells.

For this application, the research team used sEVs made by natural killer (NK) cells, a type of immune cell that often plays a role in fighting cancer. NK-derived sEVs are good at infiltrating tumors and usually contain molecules that are toxic to tumor cells. Xu and his team engineered NK sEVs with antibody fragments that strongly bind and activate DR5.

In lab dish experiments, sEVs specifically migrate and bind to DR5, rapidly killing cancer cell types with high levels of DR5 expression, including melanoma, liver cancer, and ovarian cancer cells. In experiments using mouse models of melanoma, breast cancer, and liver cancer, sEVs strongly suppressed tumor growth and prolonged survival.

Reversing tumor immunosuppression

In their experiments, Xu and colleagues observed that sEVs have other antitumor effects. The sEVs attacked other DR5-expressing cells called cancer-associated fibroblasts, as well as myeloid-derived suppressor cells that tumors use to create an immunosuppressive environment around themselves.

sEVs also stimulated T cells, further promoting the activation of anticancer immunity. Overall, the apparent ability of sEVs to subvert the immunosuppressive environment suggests that sEVs may be successful in solid tumors, where the hostile tumor microenvironment has proven challenging for many forms of immunotherapy. It suggests that.

Because sEVs are relatively easy to manufacture and store, they can be administered to any patient, making them an “off-the-shelf” treatment that eliminates the need to harvest cells from each patient, as is the case with other personalized cell therapies, Xu said. It was pointed out that there is a possibility that .

Next, the team plans to refine the manufacturing process, scale up production of clinical-grade sEVs, and conduct safety studies in preparation for human clinical trials.

Further information: Yeye Guo et al., Engineering extracellular vesicles to simultaneously target tumor cells and immunosuppressive stromal cells using DR5 agonist scFv, Science Advances (2025). DOI: 10.1126/sciadv.adp9009

Provided by Perelman School of Medicine, University of Pennsylvania

Citation: Tiny anticancer weapon: Nano-sized particles cause tumor cells to self-destruct (January 15, 2025) https://phys.org/news/2025-01-tiny-anticancer-weapon-nano- Retrieved January 15, 2025 from size.html

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