Background and objective: Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti-tumoural activities against pleural malignancies, in addition to its pleurodesing effect.
Methods: The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models.
Results: This S. aureus bio-product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm(2) vs 118.3 ± 6.7 mm(2) from saline controls at day 23, n = 9-12 per group), P < 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P < 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4(+) and CD8(+) T cells in tumour-draining lymph nodes. No histological side-effects were observed with the treatment.
Conclusions: This proof-of-principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio-products against mesothelioma.
Keywords: T cells; bacterial toxin; cytokines; malignant mesothelioma; superantigen.
© 2014 Asian Pacific Society of Respirology.