Mike Epstein
Professor Jed Macosko
Of Molecules and Machines
March 27, 2007
Cancer and Immunotoxins
Cancer is a lethal disease that kills indiscriminately. In addition to claiming hundreds of thousands of American lives each year, cancer also kills millions of impoverished people annually. In 2002 cancer took the lives of 6.7 million people globally. The disease’s future impact on humanity looks even grimmer. It is estimated that in the year 2020, cancer will claim 10.1 million lives. [1]
The developing world contributes greatly to this death toll, considering that eighty-five percent of the global population lives in developing countries. Compared to developed countries, developing countries are greatly lacking in the vital resources needed to treat cancer. Radiotherapy is a common treatment for cancerous tumors; however, developing countries contain only one third of the world’s radiotherapy facilities. Fifteen African states and several Asian states lack even one radiotherapy machine.
It is evident that the world needs a new solution for treating cancer. However in finding a solution, it is important that one understands how cancer works and why it is so deadly.
The term cancer actually refers to over one hundred separate diseases. These diseases are caused by a variety of factors. For instance, certain viruses have been linked to an onset of cancer. These viruses include the human-papillomavirus, which causes genital warts, and the Epstein-Barr virus, which causes mononucleosis. Diseases like AIDS that affect the immune system also can lead to various cancers. [3]
Certain substances called carcinogens increase the risk of getting cancer. Carcinogens like arsenic, asbestos and nickel can cause lung cancer. Tobacco is a common carcinogen which when used results in the development of various cancers, depending upon how it is ingested. Alcohol has been linked to oral cancer, and certain foods have been found to result in cancer. [4]
Furthermore, chromosomal abnormalities can contribute to cancer. Chromosomes are located within the nucleus of a cell, and carry the cell’s genetic information. When chromosomes are defective, either because they contain missing, defective or even rearranged genes, a natural predisposition to develop a cancerous tumor is increased. [5]
Cancer can develop in the healthiest of people because of various genetic mutations they may carry. One such example occurs when there is a genetic mutation in an oncogene. Oncogenes affect the way cells uses energy and multiply. A defective oncogene can contribute to the uncontrolled growth of a tumor. For instance, when the Ras gene (an oncogene) is defective it often produces proteins that cause cells to divide at an accelerated rate. [6]
Finally, mutations in tumor suppressor genes have been found to result in an onset of cancer. Tumor suppressors are supposed to prevent tumors from forming. However, when mutated these suppressors allow cells with abnormal DNA to survive and multiply. [7]
Looking at cancer’s long list of known causes, it is easy to see how one in two men and one in three women will develop cancer in their lifetimes. [8] The development of cancer starts with a basic malignant cell. Malignant cells are dangerous because they divide at a pace that is much more rapid than the pace of normal cells. These cells divide rapidly because they carry damaged genes. As the cells keep dividing, they cluster together to form a malignant tumor. [9]
Tumors cause great destruction to the body. First, they put pressure on nearby tissues and organs. The tumors can invade these organs directly through a process called direct extension, and they often damage and even disable organs. Furthermore, malignant tumors make invaded organs and tissues more susceptible to infection. Finally, tumors can destroy nearby tissues by releasing harmful substances. [10]
Tumors can thrive throughout the body. They can spread from their origin through a process called metastasis. Metastasis occurs when a tumor releases millions of malignant cells into the nearby bloodstream. Fortunately, most of these cells are killed by the immune system, or from the trauma of traveling through the walls’ of blood vessels. However, surviving malignant cells can bind to the lining of these walls. As more and more cells bind to a new location elsewhere in the body, a new tumor develops. [11]
It is clear that malignant tumors are the main threat that cancer presents to the body. In treating cancer, it is essential that these tumors be eradicated. Fortunately, drugs called immunotoxins are created for this very purpose. The job of an immunotoxin is to seek and destroy malignant tumors. One can think of an immunotoxin as a “nanoscale scalpel,” because of its ability to specifically target and kill dangerous tumors. [12]
Immunotoxins are chimeric by nature. They are composed of an antibody, which seeks out cancerous tumors, and a toxin, which kills the tumors. These two components are cloned together through recombinant DNA techniques. [13]
The antibody is an essential part of an immunotoxin. Malignant cells have a different class of proteins that are involved in cell-to-cell interaction and adhesion. Certain antibodies have the ability to bind to these proteins. The antibodies that can bind to malignant cells are determined, and cloned to a toxin of choice. [14]
Toxins alone are merely health hazards. A toxin targets indiscriminately, killing normal and malignant cells alike, causing the body great damage internally. However, when attached to the right antibody, toxins become biological tools that have the potential to destroy whole tumors. Essentially, they are “suicide nanorobots.” After binding to a cancerous cell, immunotoxins will enter and destroy it. A toxin unleashed inside a cell jumps from one molecule to the next, killing it with ease. After destroying the cell, the immunotoxin simply self-destructs. [15]
Immunotoxins are a promising treatment for cancer patients. In December, 2006, the National Cancer Institute revealed that the immunotoxin BL22 caused complete remission of hairy-cell leukemia after just three doses in half of the patients tested in a clinical trail. The BL22 immunotoxin is composed of the PE38 toxin and an antibody that binds to the receptor CD22, which is found on hairy-cell leukemia cells. The PE38 toxin is derived from a toxin produced by bacteria. It has the ability to kill human cells by blocking their ability to make new proteins. [16]
While the BL22 immunotoxin help sufferers of hairy-cell leukemia achieve remission, it does not yet have the ability to help patients with solid tumors. Leukemia causes a person to have a poor immune system; therefore patients cannot create an immune response to the PE38 toxin, and it can target cancerous cells before being struck down by the immune system. However, in patients with solid tumors who also have stronger immune systems, the PE38 is destroyed before it can make its way to these tumors. [17]
Currently researchers are cleverly working around this problem. After testing in mice which antibodies specifically reacted to the toxin, researchers have already identified sites on the PE38 that stimulate a response from the immune system. The researchers are now working on creating a strand of the PE38 toxin that lacks the amino acids that provoke a reaction from these antibodies. In creating the new and improved PE38, researchers will be able to make an immunotoxin with the potential to destroy solid tumors. [18]
Cancer ends life in a painful, torturous manner; it is difficult to understand how it can start through a single malignant cell. Nevertheless, it does and in doing so kills millions of people around the world every year. Cancer is expected to attack fifteen million people in the single year of 2020. The developing world faces nine million of these new cases, and will lack the ability to treat a majority of those afflicted. [19] Radiotherapy is costly and expensive, and often times ineffective in killing off malignant tumors; the world needs to rely on a better cancer treatment. As displayed by the BL22, immunotoxins have the potential to be the wonder drug that the world so badly needs in eradicating cancer. Immunotoxins can bring an end to malignant tumors, to cancer, and to painful deaths that millions worldwide have no alternative but to suffer through.
[1]: "Statistics for 2006." ACS. 2007. ACS. 2 Mar. 2007
[2]: "Developing World Faces Cancer Crisis." BBC. 26 June 2003. 3 Mar. 2007
[3-7]: Gordon, Jerry. "How Cancer Works." Howstuffworks. 4 Mar. 2007
[8]: "Statistics for 2006." ACS. 2007. ACS. 2 Mar. 2007
[9-11]: Gordon, Jerry. "How Cancer Works." Howstuffworks. 4 Mar. 2007
[12-15]: Goodsell, David S. Bionanotechnology: Lessons From Nature.
[16-18]: Pastan, I, and R Hassan. "NCI Researchers Develop Modified Immunotoxin for Cancer Therapy in Mouse Study." NCI. 12 Apr. 2006. 5 Mar. 2007
[19]: "Cancer Menace on the Rise." BBC. 31 Aug. 2001. 3 Mar. 2007
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