Immune mechanisms behind the Bacillus Calmette-Guerin (BCG) effectiveness against bladder cancer were revealed using a novel zebrafish model, new research shows.
The zebrafish Avatars (zAvatars) are an experimental model where tumour cells from a cancer patient are injected into zebrafish embryos, allowing the tumours to grow inside them.
This model provides a fast and personalised method to test cancer treatments, delivering results in days rather than the weeks or months required with traditional mouse models.
The research was led by Mayra Martinez-Lopez, of the Champalimaud Foundation.
Martinez-Lopez had a personal, vaunted ambition in this research. She was inspired to explore the BCG vaccine’s role in cancer after recalling her childhood vaccination against tuberculosis in South America, which has been a persistent health challenge in the country.
The BCG vaccine, originally developed against tuberculosis in the 1920s, has been used as a cancer immunotherapy since the 1970s.
Despite its empirical use, BCG remains a gold-standard treatment for early-stage bladder cancer, offering a 15-year survival rate of 60 per cent to 70 per cent.
However, 30 per cent to 50 per cent of cases are unresponsive to the treatment, often necessitating bladder removal.
The team discovered that macrophages are heavily recruited to the tumour site after BCG injection in the zAvatars.
Using light sheet microscopy and confocal imaging, they observed macrophages directly killing human bladder cancer cells via apoptosis, triggered by a substance called tumour necrosis factor (TNF) secreted by the macrophages.
When macrophages were depleted, the anti-tumour effects of BCG were completely blocked, highlighting their essential role in the immune response.
“This study not only unravels the mechanisms of BCG’s anti-tumour action but also demonstrates the potential of the zebrafish Avatar model as a powerful tool for drug discovery in oncology,” Martinez-Lopez concluded.