Experimental cancer drug targets immune cells to shrink hard-to-treat tumors in mice: study

Korean researchers said they have developed an experimental cancer drug that selectively eliminates immune cells that help tumors grow—without harming the rest of the immune system.

The treatment could open the door to more effective immunotherapies for solid tumors, such as those in the lung, colon and pancreas, which have proven difficult to treat with current immune-based approaches.

The National Research Foundation of Korea announced the development Monday, following the publication of the findings Sunday in the Journal for ImmunoTherapy of Cancer.

The drug, called TB511, is a peptide-drug conjugate—a type of molecule that links a tumor-targeting peptide to a cytotoxic payload for selective delivery. TB511 is designed to destroy tumor-associated macrophages (TAMs), a type of immune cell that accumulates in the tumor microenvironment (TME) and suppresses anti-tumor responses. Among TAMs, the M2 subtype is particularly problematic, as it promotes tumor growth, inflammation, and immune evasion.

What sets TB511 apart, researchers say, is its ability to precisely recognize and bind to an activated form of CD18, a surface protein expressed on M2 macrophages. CD18 is part of the integrin family and typically remains inactive in healthy immune cells—but shifts into an active, “open” conformation in inflammatory settings like tumors.

TB511 binds specifically to a cysteine-rich domain on CD18 that only appears when the protein is in its active shape. Once bound, the drug induces apoptosis, or programmed cell death, in the M2 macrophages—sparing healthy immune cells.

In mouse models of colon, lung, and pancreatic cancer, TB511 significantly slowed tumor growth and increased infiltration of CD8+ T cells, a key marker of anti-tumor immune activation. The drug’s effect was eliminated in models where CD18 was blocked or genetically removed, confirming CD18 as a critical driver of its mechanism, according to the study.

TB511 received approval from the Ministry of Food and Drug Safety in 2024 to begin a phase 1/2a clinical trial. Human trials are set to begin later this year.

Professor Bae Hyun-su of physiology at Kyung Hee University, who co-led the study, said the drug “precisely targets M2-type macrophages by recognizing CD18 proteins activated only within the tumor microenvironment,” adding that it could “advance both broad-spectrum immunotherapy and precision immune treatments.”