Researchers in the country have developed a drug that precisely removes only the harmful cells that hinder cancer treatment. Unlike existing immune checkpoint inhibitors that were effective only in blood cancers, this new treatment shows effectiveness against solid tumors that develop in organs, garnering attention as a next-generation cancer therapy technology.
The National Research Foundation of Korea announced on the 14th that a research team led by Professors Bae Hyun-soo and Kang Seong-ho from Kyunghee University has developed a new drug candidate that targets macrophages assisting in the growth of solid tumors. The research findings were published in the international journal "Journal for ImmunoTherapy of Cancer" on the 5th.
Immune checkpoint inhibitors are treatment methods that enhance the body's immune cells to attack cancer cells, showing excellent efficacy in specific blood cancers; however, they do not exhibit such treatment effects in solid tumors found in organs like lung cancer. This is because the tumor microenvironment surrounding solid tumors acts as a kind of barrier that hinders drug infiltration.
In particular, M2-type tumor-associated macrophages are known as key factors that suppress immunity and induce cancer progression. Macrophages are immune cells that originally consume cancer cells, but the M2-type in cancer cells actually induces cancer metastasis.
The research team focused on naturally occurring toxic substances that reduce tumor size without directly attacking cancer cells. Through the research, they discovered that this substance targets M2 macrophages and revealed that the activated CD18 protein in cells is the main binding target.
Based on this, they redesigned the molecular structure of the natural substance to develop a peptide drug candidate "TB511" that accurately recognizes the CD18 protein inside M2 macrophages while having low toxicity. TB511 does not affect normal macrophages and selectively removes only M2 macrophages within tumors.
As a result of administering TB511 to experimental animals, the growth of solid tumors such as colorectal cancer, lung cancer, and pancreatic cancer was effectively suppressed without damaging normal immune cells. The research team received clinical Phase 1/2a approval for TB511 from the Ministry of Food and Drug Safety last year and plans to conduct clinical trials involving patients starting this year.
Professor Bae Hyun-soo noted, "The drug developed this time selectively removes only M2-type macrophages by targeting CD18 activated only within the tumor," adding, "This will contribute to the future development of universal immune checkpoint inhibitors and the advancement of precise immunotherapy technologies."
References
Journal for ImmunoTherapy of Cancer (2025), DOI: https://doi.org/10.1136/jitc-2024-011422