AsianScientist (May 4, 2016) – Researchers at the School of Biomedical Sciences of Li Ka Shing Faculty of Medicine at the University of Hong Kong have recently engineered Salmonella, the bacteria that causes food poisoning, into an anaerobe bacterium named YB1. This bacterium can only survive and thrive in hypoxic regions within solid tumors, effectively inhibiting their growth without damaging healthy tissue. Their work was published in Scientific Reports.
Due to the rapid proliferation of cancer cells and inefficient tumor vascular supply, hypoxia occurs in all solid tumors as a result of an inadequate supply of oxygen. Hypoxia in tumors is associated with resistance to therapy, as it induces cellular adaptations to the stressful environment, preventing cell death and promoting the progression of tumors. This compromises the effectiveness of chemotherapy and radiotherapy.
In recent years, using bacteria as therapeutic agents against solid tumors has become an emerging field in cancer therapy research. Infections with anaerobic bacteria have been known in some cases to cause partial or complete regression of malignant tumors since the 1890’s. However, wild-type bacteria can cause severe infection, resulting in death of patients.
Combining DNA engineering with synthetic biology, the research team successfully converted the normally aerobic Salmonella typhimurium into YB1, an obligate anaerobe.
The virulence of Salmonella is preserved in YB1, but it has the additional characteristic of only being able to survive in anaerobic conditions; thus, it does minimal damage to the aerobic healthy tissue. This property makes it much safer as a clinical tool, and the researchers hope that YB1 can be further developed into a tumor-targeting agent in the near future.
YB1 has been tested in liver and breast cancer mouse models for its efficacy and safety as a cancer treatment vector. Results showed that YB1 was able to colonize the inside the tumor and effectively suppress cancer metastasis. In contrast, YB1 was quickly eliminated in healthy tissues as expected.
In a breast cancer mouse model, treatment with YB1 led to a reduction in tumor growth of 50 percent, and cancer metastasis was completely inhibited. In a liver cancer mouse model, tumor growth was suppressed by a remarkable 90 percent in the YB1 treated mice compared to the non-treated mice. Furthermore, YB1 was able to inhibit the growth of other solid tumors; for example, neuroblastoma.
In order to further improve efficacy, YB1 was equipped with different therapeutic drugs. In a breast cancer mouse model, YB1 carrying Diphtheria toxin A not only completely suppressed tumor growth but also reduced tumor size by inducing cancer cell death. In total, tumors completely regressed in 26 percent of mice treated with the bacterium. Mice treated with the bacterium were able to survive during the whole experiment which lasted for four weeks after treatment, whereas mice in the control group all died on around Day 15.
“Owing to the property that YB1 can survive in tumors, it can be viewed as a ‘guided missile’ to deliver destructive ‘warheads’ to the tumor tissue by means of delivering therapeutic proteins and drugs, resulting in tumor regression,” said lead scientist Professor Huang Jiandong.
It is estimated that YB1 will be ready for clinical trials in a few years.
The article can be found at: Yu et al. (2016) Explicit Hypoxia Targeting with Tumor Suppression by Creating an “Obligate” Anaerobic Salmonella Typhimurium Strain.
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Source: University of Hong Kong.
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