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Explore the BCG's Bladder Cancer-Fighting Mechanisms

by Karishma Abhishek on Aug 11 2024 11:49 PM
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New research using a novel zebrafish model has uncovered immune mechanisms behind BCG.

Explore the BCG`s Bladder Cancer-Fighting Mechanisms
Novel zebrafish model has helped researchers discover the immune mechanisms that make Bacillus Calmette-Guerin (BCG) effective against bladder cancer (1 Trusted Source
Scientists unravel how the BCG vaccine leads to the destruction of bladder cancer cells

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The zebrafish Avatars (zAvatars) are an experimental model where tumor cells from a cancer patient are injected into zebrafish embryos, allowing the tumors to grow inside them.

This model provides a fast and personalized 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.

Immune Responses in Bladder Cancer Therapy

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 percent to 70 percent.

However, 30 percent to 50 percent of cases are unresponsive to the treatment, often necessitating bladder removal.

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The team discovered that macrophages are heavily recruited to the tumor 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 tumor necrosis factor (TNF) secreted by the macrophages.

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When macrophages were depleted, the anti-tumor 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-tumor action but also demonstrates the potential of the zebrafish Avatar model as a powerful tool for drug discovery in oncology,” Martinez-Lopez concluded.

Reference:
  1. Scientists unravel how the BCG vaccine leads to the destruction of bladder cancer cells - (https://www.fchampalimaud.org/news/scientists-unravel-how-bcg-vaccine-leads-destruction-bladder-cancer-cells)

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