KANAZAWA, Japan, April 3, 2025 /PRNewswire/ -- Scientists at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University and colleagues have developed a promising new approach to cancer treatment. By using tiny, naturally occurring particles called extracellular vesicles (EVs), they have created a way to boost the body's immune system to fight tumors more effectively. This breakthrough could lead to more targeted cancer therapies with fewer side effects.

The study, published in Journal of Extracellular Vesicles, was led by Rikinari Hanayama. The research team developed a special type of engineered EVs, called antigen-presenting extracellular vesicles (AP-EVs), that activate immune cells inside tumors. These AP-EVs carry key immune-boosting signals, helping T cells—the body's natural cancer fighters—recognize and attack tumors more effectively. This new approach enhances immune responses while reducing harmful side effects often seen in traditional cancer treatments.

Background

Many modern cancer treatments, such as immune checkpoint inhibitors and cytokine therapies, help the immune system fight cancer. However, these treatments can sometimes harm healthy tissues and cause severe side effects. Extracellular vesicles (EVs) are tiny, bubble-like structures naturally produced by cells to communicate with each other. Scientists have recently explored their potential as a targeted drug delivery system. In this study, researchers successfully modified EVs to directly deliver immune-activating molecules to tumor-fighting T cells, improving treatment effectiveness while reducing risks.

How the Research Was Conducted

The researchers tested their engineered vesicles using cell culture experiments and mouse models, analyzing their effects with imaging, flow cytometry, and molecular assays to track immune responses and tumor growth. By observing how immune cells reacted to AP-EVs, they confirmed that these vesicles could selectively stimulate T cells and enhance their tumor-fighting ability. Advanced imaging techniques also showed that AP-EVs accumulated in tumors, making them a promising tool for targeted cancer therapy.

Key Findings

• Stronger Immune Response: AP-EVs helped immune cells grow and attack tumors more effectively.
• Changing the Tumor Environment: The treatment made tumors more visible to the immune system, turning 'cold' tumors into 'hot' ones that are easier to attack.
• Better Treatment When Combined: AP-EVs worked even better when combined with an existing immune checkpoint inhibitor (anti-PD-1 therapy).
• Potential for Human Use: Researchers successfully tested human-compatible versions of AP-EVs, showing promise for future cancer therapies.

A New Approach to Cancer Treatment

Unlike traditional immunotherapy, which can cause broad immune activation and unwanted side effects, AP-EVs provide precise targeting of tumor-fighting T cells, leading to tumor eradication without harming healthy tissue or causing other unwanted side effects. AP-EVs also have the potential to improve the effectiveness of immune checkpoint inhibitors, and other T-cell therapies.

"This discovery is an important step toward using natural biological tools to improve cancer treatment," says Hanayama, lead author of the study. "By using extracellular vesicles, we can enhance immune responses with fewer side effects, potentially leading to better outcomes for patients."

Next Steps

The research team is now working on optimizing AP-EVs for clinical trials and exploring their use for other types of cancer and personalized medicine.

Glossary

1. Extracellular Vesicles (EVs) – Tiny particles naturally released by cells that help them communicate and transfer important molecules.
2. Tumor-Infiltrating Lymphocytes (TILs) – Special immune cells that enter tumors and help fight cancer.
3. Antigen-Presenting Extracellular Vesicles (AP-EVs) – Engineered EVs that deliver immune-activating signals to T cells, improving their ability to fight cancer.
4. Interleukin-2 (IL-2) – A protein that stimulates immune cells, making them more effective at killing cancer.
5. Checkpoint Inhibitors (Anti-PD-1 Therapy) – A type of cancer treatment that helps immune cells recognize and attack tumors.

https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Eye-catching-image_JEV_2025.3.31.png

Caption: AP-EVs express molecules necessary for the activation and growth of tumor-killing T cells. Once activated, these T cells recognize tumors, secrete tumor-killing factors, and ultimately lead to tumor eradication.

© 2025 Lyu, et al., Journal of Extracellular Vesicles

Reference

Lyu, X., Yamano, T., Nagamori, K., Imai, S., Le, T.V., Bolidong, D., Ueda, M., Warashina, S., Mukai, H., Hayashi, S., Matoba, K., Nishino, T., & Hanayama, R. (2025). Direct delivery of immune modulators to tumour-infiltrating lymphocytes using engineered extracellular vesicles. Journal of Extracellular Vesicles, e70035.

DOI: 10.1002/jev2.70035

URL: https://doi.org/10.1002/jev2.70035

Funding Information

This research was supported by:

• Japan Agency for Medical Research and Development (AMED) (Grant Numbers: 22am0401019h0004, JP23ak0101178)
• Japan Science and Technology Agency (JST) (Grant Numbers: JPMJCR18H4, JPMJFR2115, JPMJPR19HA)

Contact

Kimie Nishimura (Ms)
Project Planning and Outreach, NanoLSI Administration Office
Nano Life Science Institute, Kanazawa University
Email: nanolsi-office@adm.kanazawa-u.ac.jp
Kakuma-machi, Kanazawa 920-1192, Japan

About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms".

Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.

https://nanolsi.kanazawa-u.ac.jp/en/ 

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal:

https://www.eurekalert.org/newsportal/WPI 

Main WPI program site: www.jsps.go.jp/english/e-toplevel 

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

http://www.kanazawa-u.ac.jp/en/ 

 

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