Tumor cells target metastases as they die
A new drug can eliminate cancer cells while training the immune system to destroy such cells throughout the body
Two junior research groups at Ruhr University Bochum, Germany, have developed a drug complex that kills cancer cells in such a clever manner that they raise a red flag as they die. They signal to the immune system that something is seriously wrong with this type of cell. This teaches the immune cells to destroy such cancer cells—even if they are not in the vicinity of the original tumor. This could remove metastases that develop at distant sites in the body. Dr. Johannes Karges from the Department of Chemistry and Biochemistry and Dr. Carlos Plaza-Sirvent from the Department of Medicine present their findings in the Journal of Medicinal Chemistry on July 17, 2025.
Uncommon: immunogenic cell death
90 percent of all deaths from cancer are due to metastases. This is why Karges and his team are looking for ways to train the immune system to target and eliminate cancer cells. They have found success with a drug that kills the cells in a sophisticated manner. “The gallium complex we developed penetrates the cells and, because of its special properties, causes oxidative stress in a certain cell organelle known as the endoplasmic reticulum,” he explains. “The cells then undergo immunogenic cell death, which only very few drugs can achieve.”
Immune system learns to identify cancer cells
Through this type of cell death, proteins from the endoplasmic reticulum and the cell nucleus are released to the outside and act as a strong warning signal to the immune system: Something is wrong here, these cells are harmful. This teaches the immune system to recognize the cancer cells as hostile and eliminate them throughout the body. This should also destroy metastases.
The two teams led by Johannes Karges and Carlos Plaza-Sirvent have successfully tested the active ingredient on cervical cancer cell lines. The next step is to package it in such a way that it accumulates specifically in cancer cells and is effective only there, and not in all cells of the body. Karges' research group has already developed various methods for this, for example, which active ingredients are activated by an external signal such as ultrasound or light.
Original publication
Zisis Papadopoulos, Yassin Antar, Irma-Sofie Dieter, Frank Peeters, Carlos Plaza-Sirvent, Johannes Karges: Gallium(III) Complex Induces Immunogenic Cell Death Hallmarks for Chemoimmunotherapy, in: Journal of Medicinal Chemistry, 2025
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