Cancer is one of the most difficult sickness to cure and more often than not incurable. Recent researches however have been conducted to provide a cure for cancer by using genetic manipulation to kill cancerous cells in the body of a cancer patient. Positive results of the studies conducted were encouraging – however experimentations are still limited to animals and not widely applied to humans. Nevertheless, such medical attempts are breaking ground for successful cancer treatment and prevention.
In September 2007 issue of Science Daily, an article entitled Re-engineered Human T Cells Effectively Target And Kill Cancerous B Cells, presented a recent finding showing that modified T cells (white cells that actively fight infections) can be effective in fighting malignancies caused by B cells (immune cells) like the chronic lymphocytic leukemia (CLL). The idea is to induce a repeated dose of T cells designed to express an artificial receptor which recognizes human B cells. The findings showed that they were able to eliminate forty four percent cancer cells on mice carrying human tumors.
Dr. Brentjens, a medical oncologist in the Leukemia Service of Memorial Sloan-Kettering Cancer Center (MSKCC), and his colleagues used an engineered retrovirus to insert the chimeric antigen receptor gene into T cell DNA. Retroviruses insert DNA derived from their RNA into that of a host cell, which then uses viral vector-encoded genes to make specific proteins. In this case, the researchers infected healthy T cells with modified retroviruses containing the gene that codes for 19-28z.
The T cell’s internal protein-making facilities then produce the chimeric receptor as if it were one of its own natural antigen receptors. By taking a patient’s own T cells, and re-educating them (by inserting a gene into them that will enable them to produce a receptor to recognize B cell cancers) the T cells are then returned to the patient to attack and kill the tumor cells. Since the procedure is using a patient’s own T cells, there is little risk of compatibility issues or rejection, as there might be with human stem cell transplant.
Human stem cell transplant, following radiation or chemotherapy, is currently incorporated into the treatment of several B cell malignancies. This concept of T cell persistence is subject for further investigation in current and upcoming clinical trials. Scientists from the University of California, San Diego (UCSD) School of Medicine and Cancer Center presented findings about Telomerase (an enzyme that maintains normal chromosome length during cell replication). Telomerase is considered as the first gene to play a direct role in tumor transformation of cells by allowing precancerous cells to become immortal.
The article UCSD Team Demonstrates Potential For Widely Effective Cancer Vaccine mentioned a team led by Maurizio Zanetti, a UCSD professor of medicine and member of the UCSD Cancer Center. They successfully used a prototype vaccine in cancer cells and aimed to activate a type of lymphocyte called cytotoxic T-lymphocytes (CTL), or killer cells, to destroy cancer cells using telomerase as a target. Lymphocytes are white blood cells around the body that launch an attack against the invader once attacked. . Killer cells target infected or cancerous cells by recognizing and binding to proteins, or antigens, on the cell surface.
In cancer, the immune system becomes weakened against rapidly growing malignant cells. “We wanted to see if the immune systems of individuals with cancer retained the ability to recognize telomerase, and if we could boost the immune response using telomerase in a prototype vaccine to expand CTL activity against cancer,” mentioned Zaneti (2000). They observed that lymphocytes from prostate cancer patients were readily activated into CTL following immunization with the prototype vaccine, attacking and killing the cancer cells.
They added CTL produced in the prostate cancer cell samples to other human cancer cells–breast, colon, lung and melanoma–and found that the killer cells targeted the hTRT peptides in these cells as well and destroyed them. Experiments also were conducted using transgenic mice provided by the Institut Pasteur in Paris. These mice are genetically engineered to mimic the human immune system, expressing a common type of human transplantation antigen. The prototype telomerase vaccine applied to mice showed no apparent negative side effects, demonstrating the potential of this vaccine in a live model.
The team also found out no adverse activity detected in human cells. They predicted that since telomerase level in normal cells is low, there is little danger that this approach would cause an autoimmune reaction, with the body attacking its own normal cells. However, they acknowledged other potential problems and require further study. These promising results indicate that telomerase should be further studied as the basis of a vaccine against many types of cancer, activating the body’s own defense system and serving as a flag to draw CTL to the cancer cells.
The application of genetic manipulation in cancer treatment and prevention bore positive results and findings. Scientists though are careful to conduct experiments to humans despite positive effects conducted to experimental animals, because of unforeseen detrimental effects it may have on the human body. However, encouraging positive results of recent studies conducted are indicative of a possible cancer vaccine or treatment in the future that may help many cancer patients, thus such attempts will serve as a breakthrough in defeating cancer and benefiting countless cancer patients worldwide.