A breakthrough in cancer immunotherapy has emerged from a research team led by Professor Yoosoo Yang at Sungkyunkwan University, in partnership with the Korea Institute of Science and Technology and Incheon National University. The team has engineered an innovative method to selectively manipulate tumor-derived extracellular vesicles (TEVs), nanoscale particles secreted by cancer cells known to influence tumor progression and immune response.
TEVs have a dual role in cancer biology: while they can facilitate tumor growth and metastasis, a subset of these vesicles also has the ability to activate antitumor immune responses. Conventional pharmacological approaches, which broadly inhibit extracellular vesicle production, risk suppressing these beneficial vesicles along with the harmful ones, limiting therapeutic outcomes.
To overcome this challenge, the researchers introduced a groundbreaking strategy called “Switching TEVs Off and On,” enabled by a novel nanoswitch-based agent named EVOTAC. This agent selectively degrades key intracellular proteins to halt the secretion of tumor-promoting vesicles, effectively resetting the tumor microenvironment. Subsequently, localized photodynamic therapy, involving laser activation of a photosensitizer, reactivates the tumor cells to produce immunogenic TEVs that stimulate anticancer immunity.
The mechanism leverages the photodynamic therapy’s generation of reactive oxygen species to induce a shift in vesicle composition. Upon laser treatment, tumor cells preferentially release extracellular vesicles enriched with molecules that enhance immune recognition and attack against cancer cells, effectively “switching on” the body’s defenses.
In preclinical models of aggressive cancers such as triple-negative breast cancer and colorectal cancer, this precision nanoswitch approach achieved complete tumor eradication. Moreover, the therapy elicited robust immune activation that suppressed both recurrence and metastasis, marking a significant advance over existing strategies.
This pioneering work demonstrates for the first time that tumor-derived extracellular vesicles can be precisely manipulated as both therapeutic targets and immune modulators, ushering in a new paradigm for cancer immunotherapy. By transforming the tumor microenvironment through selective control of vesicle populations, this approach holds promise for improving long-term outcomes in hard-to-treat cancers.
The findings, supported by the Ministry of Science and ICT’s Bio & Medical Technology Development Program, were published in the prestigious journal Signal Transduction and Targeted Therapy. This study paves the way for future research focused on nanoscale manipulation of intercellular communication to combat cancer more effectively.
As the field moves forward, EVOTAC and the “Switching TEVs Off and On” strategy represent a conceptual and technological breakthrough with potential to inspire innovative treatments that harness the complexity of tumor biology and immune dynamics.
Subject of Research: Cancer Immunotherapy, Tumor-derived Extracellular Vesicles
Article Title: Switching tumor-derived extracellular vesicles off and on via targeted proteolysis to shift toward immunogenic phenotypes
Web References: http://dx.doi.org/10.1038/s41392-026-02872-5
Image Credits: Jang, Y., Park, B., Choi, J. et al. Signal Transduct Target Ther 11, 266 (2026)
Keywords: Cancer Immunotherapy, Extracellular Vesicles, Tumor Microenvironment, Photodynamic Therapy, Nanoswitch, EVOTAC
