Pancreatic cancer is the fourth leading cause of death and it`s because it is a silent killer and there is only a five year survival rate of 4 percent of the patients. Before the primary tumor is detected, metastasis has already spread to other parts. The current treatment options involve the removal of the tumor then followed by chemotherapy or radio therapy and the use of drops like Gemcitabine and Erlotinib.
There are different types of metastasis therefore there are other treatment alternatives to be sought after hence the option of radioactive listeria monocytogene which is a bacteria used as a deliberate system. This is used because our immune system can`t fight off cancer cells since they can`t recognize them and the bacteria listeria expresses antigens as expressed by the cancer cells. These foreign cells are therefore recognized.
The vaccine containing the listeria monocytogenes have them cloned so that they are recognized. The LLO allows listeria to escape from the vaccine to the other cell. This triggers a new immune response. The cytogenes cells where the listeria bacteria have expressed can be spotted and hence the cell can be killed. The listeria particularly goes to the infected cells that need to be recognized.
The listeria could be located in the tumor and in the metastasis and hence we not only use listeria to express the antigens but also to deliver agents that can kill the cancer cells as it multiplies. The listeria bacteria multiply in the tumor and the metastasis but not in the normal cells. The confirmation of the presence of listeria is by the confocal microscopical analysis done in vivo.
The listeria has a premotor control that directs listeria to escape to cancerous cells. The survival time for listeria is about three to five days then eliminated from the system. This bacterium has been used in clinical trials sensitive for penicillin and derivatives.
The radio isotope emits cytocidal radiation which is beta particles inducing ROS and it is coupled to listeria through the anti-listeria antibodies. The resultant effects of listeria include; induces high presence of ROS hence damaging DNA in high proliferating cells causing cell death and this is also similar to radioactive induced listeria.
In an experiment where pancreatic cells in the mammary are used after being injected with tumor cells in three weeks the cells have developed pancreatic tumor and metastasis. The isotope used doesn’t kill t5he listeria, it doesn`t alter the stability of listeria to hinder its performance, and the isotope 188Re does not alter the infection rate of listeria.
For the experiment with mice without tumors listeria is found in very minimal amounts and it is eliminated but for a comparison with mice with tumor cells, listeria is found in metastasis in large amounts and also in tumor cells. The radioactive counts in both the mice with or without tumors are undetectable in all tissues on day 7 after the introduction of the material into the system.
The number of metastasis contained in mice without treatment is high and after listeria injection, there is a 40 percent reduction in metastasis. The listeria with radioactive material reduces the metastasis count is reduced up to below 25 percent. The resultant effect of a radioactive listeria in low proliferated cells is low because they are in a base dormant tissue. In the portal liver, the metastasis is almost completely eradicated by the radioactive listeria.
Radioactivity listeria is selectively accumulates in the metastasis and this occurs around the liver and kidney because they are responsible for metabolism and excretion and hence the radioactive material will pass through the organs. After 11 treatments with radioactive listeria, and despite accumulation of radioactive material in the kidneys and liver, no pathological damage was observed in the tissues hence the radioactive listeria does not affect tissues after treatment. The liver functions and kidney functions were found to be as normal as before.
The CD8 T cells were found not to contribute to the radioactive effect on metastasis.
Conclusion
After the experiment, it was deduced that listeria multiplies in metastasis and tumor cells but not in normal unaffected issues and the radioactive listeria extensively reduced the number of metastasis after 11 treatments carried out with low dose of the radioactive listeria (10,000 × below LD50). It is also noted that the CD8 cells do not contribute to the reduction in the number of the metastasis by administering the radioactive listeria treatment.
In a highly aggressive pancreatic cancer model, the radioactive treatment is particularly aggressive and the radioactive treatment does not harm normal cells despite the accumulation of the radioactive isotopes.
The future prospects will involve the testing of higher doses of the radioactive listeria and other treatment strategies and also the incorporation of phosphorous 32 into cell wall of listeria. Other radio isotopes such as 213Bismuth, 177Luthetium will be tested and the improvement of the safety aspects of the research together with the advancement to the clinical trials of the treatment.
