A new method to develop personalized vaccines to treat patients' diagnosed ovarian cancer has been found by the researchers at the University of Connecticut. They have discovered a way to identify protein mutations in cancer cells and the same will prove vital in developing the said vaccine.
Dr. Pramod Srivastava, director of the Carole and Ray Neag Comprehensive Cancer Center at UConn Health and one of the principal investigators on the study remarked that the way we treat cancer will be dramatically changed once the experiment is successful. He added that this research is going to the basis for the first ever genomics-driven personalized medicine clinical trial in immunotherapy of ovarian cancer. The same is scheduled to begin this fall at UConn Health this fall. Ion Mandoiu, an UConn bioinformatics engineer associate professor of computer science and engineering along with other principal investigator for the study has been working on the research for the past four years. The results of the study were published online in the 22 September issue of the Journal of Experimental Medicine.
Srivastava added that it has been known that patients have genetic sequences that make them better candidates for some drugs than others. Today there are means to figure that out much more easily now than five years ago. If this novel approach proves to be safe and effective, it would be the ultimate in individualized medicine.
Dr. Angela Kueck, a gynecological oncologist at UConn Health, is going to be in charge for running the initial clinical study. The approval from FDA for the same is awaited. The research team will be sequencing DNA from the tumors of 15 to 20 women diagnosed ovarian cancer. The information from the same will be used to develop a personalized vaccine for each woman.
There is a reason why researchers chose to perform the clinical trial on patients with ovarian cancer. It is seen that in short term the disease typically responds well to surgery and chemotherapy. However, after a year or two it returns lethally. The researchers opined that they will have a window of 1-2 years to prepare and administer the new therapeutic vaccine and in the said time they would be able to conclude if the vaccine made any difference in the patients. For the next steps in the trail, it has been decided that if the personalized vaccines are found to be safe and feasible, they’ll design a Phase II trial. In this phase the clinical effectiveness of the drug in prolonging patients’ lives will be evaluated.
For the immune cells to attack cancer cells, it need to recognize them, On every cell's exterior there is a sequence of protein which acts like an Id card which tells it the particular cell is a normal one or not. These protein sequences are called epitopes and this is what the immune system looks for in a cell. The cancer cells have epitopes too and they are similar to the healthy cells. That is why the immune system is unable to recognize them and hence take no action on it.
The cancer cell epitopes have some subtle difference from the normal cell epitopes and that is what can give them away. However, the key thing for it is that the immune cells must know what to look for. Srivastava added that there may be 1000 minute changes, but of them only 10 are important from the perspective of the immune system. To find out what the important differences are, Mandoiu, the bioinformatics engineer, took DNA sequences from skin tumors in mice and compared them with DNA from the mice’s healthy tissue.
It was seen that when the mice were inoculated with vaccines made of the cancer epitopes differing the most from normal tissue, they were very resistant to skin cancer. It is speculated that theoretically, this approach could work for other cancers too. However, more research is needed for the same.