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Fighting Cancer with Radioactive Listeria-The Lesser of Three Evils?
Scientists have combined a dangerous pathogen and a radionuclide as a treatment for a yet deadly disease. A group of researchers at the Albert Einstein College of Medicine in New York, claim to successfully defeat Pancreatic Ductal Adenocarcinoma, commonly known as pancreatic cancer, with live attenuated Listeria monocytogenes labelled with a radioactive Rhenium isotope (188 Re). This radioactive bacterium injected into mice in which aggressive pancreatic cancer has been induced, killed the tumor cells without causing severe side effects.

A Silent Killer

Pancreatic cancer, the fourth leading cause of cancer deaths today, is difficult to control due to the distribution of cancer cells to other organs (i.e. metastasis) before the primary tumor is detected. This results in tumors in other parts of the body. These secondary tumors or metastases are resistant to chemotherapy and difficult to remove by resection or external radiation. Therefore, current cancer treatments such as surgery, radiation and adjuvant therapy which are successful against most cancers have not been effective against pancreatic cancer. An effective long-term treatment for this disease is virtually non-existent since the FDA approved-anti-cancer drugs, Gemcitabine and Erlotinib can only increase the survival period by about 6 months.

Targeted-Radionuclide Therapy

Radionuclide therapy is considered a promising treatment against several cancers. Tumor-targeting vehicles such as small molecules, monoclonal antibodies and peptides etc., which are labelled with radioactive elements, can be used to deliver radionuclides to the target tissues where they emit cytotoxic radioactive particles that physically destroy the tumor cells. However, previous trials using tumor-specific antibodies to deliver radionuclides on treating pancreatic cancer with revealed to have limited success. Hence, there exists the need of finding an effective mode of transporting the treatment into the tumors.

A New Delivery Vehicle: Dangerous but Convenient

Listeria monocytogenes is one of the most virulent food-borne pathogen responsible for Listeriosis, a disease that can be fatal. Nonetheless, L. monocytogenes, genetically engineered to remove their virulent factors, have been used as a vector to deliver therapeutics in patients with cystic fibrosis and cervical cancer. In a previous study, the researchers revealed that the attenuated Listeria monocytogenes cells have the ability to selectively accumulate in the tumors and kill the tumor cells by secreting high levels of reactive oxygen species.

Although unable of causing disease, these live attenuated Listeria cells can infect and spread within the cells. Researchers found that the immune system efficiently cleared the attenuated Listeria cells from the normal tissues but in the in metastases and primary tumors where the immunity is suppressed these bacteria piled up considerably. This phenomenon offered a solution as a new means of effectively delivering targeted nuclides into tumors

Radioactive Bugs

In the current study, the attenuated Listeria coupled with radioactive Rhenium isotope were used to treat pancreatic cancer in a mouse model. 188 Re was attached to the bacterial cells using 188 Re-labeled anti-Listeria antigens. 188 Re was the radionuclide of choice due to its short half-life that enabled it to deliver the radiation dose within a shorter time, matching the vigorous growth of the cancer cells.

During the study, it was confirmed that viability and the genetic stability of the attenuated Listeria was not significantly reduced upon labelling with 188 Rh. Furthermore, labelling with radionuclides found to increase the infection rate of the bacteria.

Higher Success Rates

These radioactive Listeria (RL) were then injected into mice in which highly metastatic pancreatic tumors were generated. High levels of radioactivity were observed in metastases while the radioactivity measurements were lower in the primary tumors and normal tissues. One week after the treatment, the radioactive readings in the tissues dropped to lower than detectable levels and the attenuated Listerial cells appeared to be eradicated from the tissues by the immune system.

The scientist declare that the treatment considerably reduce the number of metastases in diseased mice without causing any side effects.

A Note of Caution

The researchers found that the livers and kidneys of the infected mice also accumulated levels of radiation as high as in metastases. They hypothesised that this is because the remnants of radioactive materials which were transferred to the liver following destruction by the immune system, were collected in the kidneys until excretion. However no pathological damage was observed in the liver or kidney cells and liver functions were unaffected.

Nevertheless, more research ought to be carried out before testing the treatment on humans.

Source :

Quispe-Tintaya, W., Chandra, D., Jahangir, A., Harris, M., Casadevall, A., Dadachova, E., & Gravekamp, C. (2013). Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer. Proceedings of the National Academy of Sciences, 110(21), 8668-8673.
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