Macrophages in the tumor. Photo: University of Turku

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Researchers from the University of Turku's InFLAMES flagship program have made a breakthrough in cancer treatment with the development of Beksmarilimab, a new drug that reactivates white blood cells within tumors that have been hiding from the immune system. This promising discovery offers a new avenue for cancer immunotherapy, particularly for patients who have shown a favorable response to the drug.

Beksmarilimab works by awakening macrophages, a type of white blood cell, within the tumor. These cells then alert other cancer-fighting cells to the tumor's presence. Traditional cancer immunotherapies focus on enhancing the body’s defense system, often targeting T-cells. However, these therapies don't work for all patients, underscoring the need for novel treatments like Beksmarilimab.

Macrophages usually play a role in destroying cancer cells, but tumors can suppress their activity, allowing the cancer to remain undetected by the body's immune system. Beksmarilimab, however, can alter the function of tumor-associated macrophages, prompting them to activate other cells in the immune system to fight the cancer.

Dr. Maija Hollmén and her research team have been studying how Beksmarilimab affects white blood cells within the tumors of patients who have received the drug. Clinical trials revealed Beksmarilimab to be a well-tolerated form of treatment that stabilized or improved the condition of some patients. Those who showed slower disease progression under treatment exhibited increased activation of tumor macrophages, lymphocytes, and a rise in interferon, a crucial messenger in anti-cancer immune defense, in their bloodstream.

Spatial transcriptomics, a method that provides information on gene expression in microscopic areas of tissue samples, such as individual types of white blood cells, was used to study the activated defense cells in patients’ cancer tissues.

The variability in how patients' white blood cells respond to treatment and the cancer tissue's resistance to immune-activating therapies highlight the importance of identifying which cancer types respond best to new treatments like Beksmarilimab.

Hollmén's team used cell culture conditions to further understand how individual white blood cells react to the treatment. They observed the same defensive reaction that occurred in patients' tumors: Beksmarilimab awakens macrophages, which can then activate the body's killer cells, T-lymphocytes.

Jenna Rannikko, the lead author of the studies, notes that for an effective response, cooperation among various types of white blood cells is necessary. The team also discovered that macrophages previously exposed to interferons are resistant to Beksmarilimab. This suggests that Beksmarilimab could be most effective in tumors where current immunotherapies perform poorly due to low interferon levels and the cancer's ability to evade immune attacks.

Developed by the Turku-based pharmaceutical company Faron Pharmaceuticals, Beksmarilimab's research findings were published in the prestigious journals Cell Reports Medicine and Cancer Immunology Research in late 2023. The drug's success in altering the immune system's activity in tumors unresponsive to current treatments holds significant potential for enhancing the efficacy of existing immunotherapies.

HT

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