Researchers at Penn Medicine have created an innovative cancer treatment using nano-sized capsules that can target and trigger cancer cell self-destruction, which could reshape cancer immunotherapy.
The experimental approach — which is progressing toward advanced testing — centers around small extracellular vesicles, tiny capsules engineered in the lab from human cells. These vesicles are designed to target a particular receptor called DR5 found on the surface of many tumor cells. When activated, the receptor can initiate a process known as apoptosis, where cancer cells essentially self-destruct.
“This new strategy has a number of advantages compared to previous DR5-targeting strategies and other anticancer immunotherapies,” Professor of Pathology and Laboratory Medicine Xiaowei “George” Xu said. “After these encouraging preclinical results, we’re developing it further for human clinical trials.”
In preclinical tests, Penn Medicine's engineered small extracellular vesicles not only outperformed previous DR5-targeting strategies, such as antibodies, but also demonstrated strong anticancer effects. The sEVs showed remarkable success in lab-dish experiments, efficiently targeting various cancer cell types, including melanoma, liver, and ovarian cancer. Furthermore, in mouse models, the sEVs significantly suppressed tumor growth and prolonged survival, suggesting their potential as a more effective treatment option.
The therapeutic benefits of sEVs go beyond targeting cancer cells. The vesicles can also attack certain cells that contribute to the environment tumors create to shield themselves from the body's immune system. By disrupting this immunosuppressive environment, the sEVs boost the body's natural immune response, providing an additional layer of defense against tumors.
Moreover, the sEVs' ability to stimulate T cells, key players in the immune system's fight against cancer, further enhances their potential as an immunotherapy. This suggests that the engineered sEVs could be particularly effective in treating solid tumors, where traditional immunotherapies have struggled.
Since sEVs can be manufactured and stored easily, this potentially provides a therapy that could be ready for immediate use without the need to harvest cells from individual patients. The therapy could dramatically simplify the treatment process and make it more accessible to a wider range of patients.
Following these promising preclinical results, the team plans to refine the manufacturing process to scale production for clinical grade sEVs and conduct safety studies in preparation for human clinical trials.
“We’ve seen that many patients have benefited from advances in cancer immunotherapy but know there’s more to work to do,” Xu said. “This is our motivation for seeking new strategies for cellular therapies.”
The study, funded by the National Institutes of Health, might provide patients with more effective options to combat cancer and, ultimately, improve outcomes.
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