A team of Korean researchers has developed a novel peptide-based drug that selectively eliminates tumor-promoting immune cells, paving the way for a new strategy to treat hard-to-cure solid tumors. The study, published in the Journal for ImmunoTherapy of Cancer in April 2025, was led by Professor Hyunsu Bae and Seong Ho Kang of Kyung Hee University.

The new drug, named TB511, specifically targets M2-like tumor-associated macrophages (M2-TAMs); a major population of immunosuppressive cells that constitute up to 40% of the tumor mass in many solid tumors. These cells promote tumor growth, help cancer evade immune responses, and contribute to the failure of existing immunotherapies.

Unlike previous treatments that lack selectivity and often harm healthy immune cells, TB511 binds to an "activated form" of the CD18 protein, which is uniquely existed on the surface of M2-TAMs. This allows the drug to induce cell death in M2-TAMs without affecting normal immune cells.

In preclinical studies, TB511 significantly suppressed tumor growth in colorectal, lung, and pancreatic cancer models. Moreover, it reprogrammed the tumor microenvironment (TME) from an immunosuppressive state to an immune-activating one, thereby enhancing T-cell-mediated antitumor activity.

“This is the first drug that can precisely target and eliminate the ‘bad’ macrophages inside tumors,” said Professor Bae. “By doing so, we believe it can overcome the major limitation of current immunotherapies, which often fail in solid tumors.”

Following regulatory approval, clinical trials (Phase 1/2a) began in 2024. The research team also sees broader applications for the platform, including diseases driven by dysfunctional macrophages such as pulmonary fibrosis and MASH (Metabolic dysfunction-associated steatohepatitis).

“Our ultimate goal is to develop a new platform for precision immunotherapy; not only for cancer but also for a wide range of intractable diseases,” Prof. Bae added.

Mechanism of action of the peptide drug TB511 in the tumor microenvironment

[Reference] Bae H. et al., (2025) “Conformation-sensitive targeting of CD18 depletes M2-like tumor-associated macrophages resulting in inhibition of solid tumor progression.” Journal for ImmunoTherapy of Cancer. DOI: 10.1136/jitc-2024-011422

[Main Author] Hyunsu Bae (Kyung Hee University, Seoul, Korea), Seong Ho Kang (Kyung Hee University, Seoul, Korea), Ik-Hwan Han (Kyung Hee University, Seoul, Korea), Ilseob Choi (Kyung Hee University, Seoul, Korea)

* Contact :Professor Hyunsu Bae; hbae@khu.ac.kr