Precision Nanobody Targets Lung Cancer Tumors

National Research Council of Science & Technology

A research team led by Dr. Juyeon Jung at the Bio-Nano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , has developed a nanobody-based technology that can precisely identify and attack only lung cancer cells, opening new possibilities for cancer therapy.

This breakthrough addresses the limitations of conventional chemotherapy by reducing harmful side effects while maximizing cancer cell-killing efficiency. In particular, it shows remarkable therapeutic potential for lung adenocarcinoma, a subtype of non-small cell lung cancer (NSCLC).

Lung cancer is one of the world's deadliest diseases, claiming millions of lives each year. Among its types, lung adenocarcinoma accounts for over 50% of cases and is characterized by late detection and high recurrence rates. Current chemotherapies often attack healthy cells as well, leading to severe side effects such as hair loss, nausea, and immune suppression, and frequently fail to deliver drugs precisely to cancer cells, reducing treatment effectiveness.

To overcome these challenges, the team developed the A5 nanobody — a miniature antibody that binds specifically to CD155, a protein found in high abundance on lung cancer cells. The A5 nanobody is roughly 10 times smaller than conventional antibodies, enabling it to penetrate deep into tissues. It binds selectively to cancer cells without affecting healthy cells, inhibiting lung cancer cell migration and invasion by more than 50%.

The researchers also engineered A5-LNP-DOX, which combines the A5 nanobody with liposomal capsules containing the anticancer drug doxorubicin (DOX). This design acts like a "drone strike", delivering the drug precisely to CD155 targets on the surface of cancer cells.

In experiments, A5-LNP-DOX delivered up to three times more drug into cancer cells than conventional methods, significantly enhancing cancer cell death while leaving healthy cells largely unharmed.

Tests in animal models and patient-derived organoids showed tumor size reductions of 70–90% and substantial increases in cancer cell death markers. No damage was detected in major organs such as the liver, heart, or kidneys, indicating a highly safe treatment profile.

Dr. Juyeon Jung, the lead researcher, stated,

"Our study presents a new therapeutic strategy capable of precisely targeting cancer cells and delivering drugs effectively," She added, "We expect this nanobody-based approach to serve as a versatile platform for treating not only lung cancer but also a variety of other cancers, contributing greatly to the advancement of precision medicine."

Korea Research Institute of Bioscience and Biotechnology (KRIBB) is a leading national research institute in South Korea dedicated to cutting-edge research in biotechnology and life sciences. Established in 1985, KRIBB focuses on advancing scientific knowledge in areas such as molecular biology, genomics, bioinformatics, synthetic biology, and aging-related studies. As a government-funded institute, KRIBB plays a pivotal role in driving innovation, supporting national R&D strategies, and collaborating with academic and industrial partners both domestically and internationally.

This research was supported by the Basic Research Program of the Ministry of Science and ICT(MSIT) and the Technology Commercialization Support Program of the Korea Agency of Education, Promotion and Evaluation for Food, Agriculture, Forestry and Fisheries(IPET), as well as KRIBB Research Initiative Program

The study was published online on July 10, 2025, in the prestigious international journal Signal Transduct Target Therapy (Impact Factor: 52.7) under the title: "Targeting CD155 in lung adenocarcinoma: A5 nanobodybased therapeutics for precision treatment and enhanced drug delivery"

(Corresponding Authors: [KRIBB] Dr. Juyeon Jung)

(First Authors: [KRIBB] Dr. Kyunghee Noh, Soyeon Yi)

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