Researchers at the University of Turku in Finland have made a breakthrough in understanding how the newly developed cancer drug, bexmarilimab, is able to modify immune cell function, enabling them to penetrate tumors in cancer patients resistant to existing therapies. The innovative therapy, developed by Faron Pharmaceuticals, has been detailed in research publications in Cell Reports Medicine and Cancer Immunology Research.
Bexmarilimab represents a promising advancement in cancer immunotherapy, a field leveraging the body's own immune system to combat cancer. For patients who do not respond adequately to current immunotherapies, novel approaches like bexmarilimab are crucial.
This experimental cancer therapy focuses on altering the behavior of macrophages, versatile immune cells that cancer often exploits to evade detection by the immune system. Docent Maija Hollmén's research group at the InFLAMES Research Flagship, affiliated with the University of Turku, delved into the mechanisms through which bexmarilimab influences immune cell function within the tumors of patients.
“In an advanced-stage cancer clinical trial, bexmarilimab demonstrated good tolerance and exhibited disease progression stabilization in specific patient subsets. Notably, patients benefiting from the therapy displayed activation of tumor-associated macrophages and lymphocytes, along with the induction of interferons – key indicators of anti-tumoral immune defense,” explains Dr. Hollmén.
The research employed an innovative spatial transcriptomics method, enabling scientists to examine changes in the gene expression of immune cells within the spatial context of patient tissue samples. This approach provides valuable insights into the intricate interactions occurring at the cellular level, contributing to the growing understanding of bexmarilimab's potential in reshaping the landscape of cancer therapy.
Efficacy in tumors resistant to current immunotherapies
Differences in sensitivity to immunotherapies among individual cancer patients highlight the need to pinpoint tumor types with the highest response to novel treatments. Recognizing that tumors exhibit varying degrees of resistance to immune attacks, researchers, led by Docent Maija Hollmén's group at the University of Turku, focused on understanding the efficacy of the innovative immunotherapy, bexmarilimab.
In meticulous studies involving patient-derived cancer cells and immune cells treated with bexmarilimab in cell cultures, the research team closely examined how individual immune cells respond to this therapy.
“We observed consistent activation of the immune system in patient-derived cell cultures, mirroring our findings within patient tumors. Bexmarilimab stimulates macrophages, which, in turn, activate T lymphocytes proficient in eliminating cancer cells. The success of the treatment hinges on the collaborative efforts of multiple immune cell types,” explains Jenna Rannikko, the first author of the related research articles.
The striking parallels between the clinical study and patient-derived cell cultures prompted the group to delve into the factors contributing to the variable efficacy of bexmarilimab in different patients. Their investigation revealed that interferon exposure prevents bexmarilimab from activating macrophages.
This discovery holds significant implications, suggesting that bexmarilimab could be most effective in tumors where current immunotherapies demonstrate limited success. Such tumors typically exhibit lower levels of interferons. Following bexmarilimab-induced anti-tumoral immunity, these tumors might become more responsive to currently available immunotherapies.
Source: University of Turku