Australia’s long history with asbestos has given it the distinction of having one of the highest rates of mesothelioma in the world. It is also the location of some of the most cutting-edge mesothelioma research.
The latest study, conducted by the School of Pathology and Laboratory Medicine at UWA and published in the Journal of Interferon and Cytokine Research, suggests that a “cocktail” of drugs to simulate the immune system can eradicate mesothelioma tumors. The researchers used a timed triple immunotherapy (TTI) protocol of three antibodies designed to “turn off” the production of specific proteins associated with cancer.
Three Targeted Proteins
Three proteins were targeted by the drug cocktail. The first, CD25, is present on activated immune system T-cells and B-cells. The second protein, TGF-β, controls proliferation and cellular differentiation and is known to play a role not only in cancer, but also in asthma, heart disease, diabetes, and AIDS. The third targeted protein was CTLA-4, a protein found on the surface of T-cells which downregulates the immune system. By using drugs that deactivate these three proteins, the Australian research team managed to cure mice of their mesothelioma tumors.
“We report that a timed triple immunotherapy protocol using 3 agonist antibodies produced complete clearance of established AB1 murine mesothelioma tumors,” reports Shruti Krishnan, the paper’s lead author. Krishnan and her colleagues also found that combining the three antibodies into a single “cocktail” was just as successful against mesothelioma in the mice as giving the antibodies in succession.
B-Cells and Immunotherapy
When the cured mice were tested after three months, they were found to have higher levels of immunoglobulin G, an immune system antibody secreted by B-cells. There were also more B-cells in the lymph nodes closest to the tumors and in the spleen, suggesting that B-cells may play an important role in the success of this immunotherapy approach to mesothelioma.
Immunotherapy is an emerging treatment protocol for mesothelioma and other cancers designed to stimulate the host’s immune system to destroy cancer. The promise of immunotherapy treatment is especially important for mesothelioma patients because the disease is highly resistant to standard therapies.
Krishnan, S et al, “Successful Combined Intratumoral Immunotherapy of Established Murine Mesotheliomas Requires B-Cell Involvement”, September 26, 2014, Journal of Interferon and Cytokine Research, Epub ahead of print