A big step towards the approval of an experimental treatment for advanced cancer through an upgrade of the patient’s immune system cells: managed to reduce the metastases and resulted in a remission of the disease
Researchers isolated immune cells from metastases of skin cancer patients, modified them and put them back into the patients’ bodies. The clinical trial, the findings of which were published in the New England Journal of Medicine, showed good success in curbing the disease. Not only may it lead to a remission of the disease and prolong the lives of the patients, but it has even shown superiority over one of the medical treatments accepted today.
Melanoma skin cancer is a very violent and dangerous type of cancer, because the diseased cells tend to detach from the primary tumor, spread and send metastases to distant organs such as the lungs, liver and bones. 15 percent of those diagnosed develop metastases. Until a decade ago, metastatic melanoma was considered a terminal disease, with a life expectancy of only a few months from the moment of diagnosis. Despite considerable improvement since then in the treatment of the disease, still only about 30 percent of advanced melanoma patients (stage 4) survive more than five years after diagnosis.
All types of cancer have several stages in the development of the tumor and its spread. In the most advanced stage, stage 4, the tumor has already outgrown its initial location and has metastasized to other organs. As the tumor is in a more advanced stage, the chances of recovery from it decrease and the methods of treatment also change accordingly. Metastatic melanoma is rarely treated with standard chemotherapy drugs, because their effectiveness at this stage is very limited. Therefore, it is very important to develop new methods to treat the disease.
Fifteen percent of those diagnosed develop metastases. A melanoma lesion in the skin metastasizes to the blood and lymph Illustration: Christoph Burgstedt, Science Photo Library
treat the immune cells
In a new study, researchers from the Cancer Institute in the Netherlands and researchers from the National Center for Immunotherapy in Denmark improved the function of immune system cells that specialize in eliminating diseased cells and cancer cells. As part of the treatment, cells of the immune system, called “tumor-infiltrating lymphocytes” (Tumor-Infiltrating Lymphocytes), were isolated from a sample taken from one of the tumor’s metastases, and replicated in billions of copies. This ensured that the cells knew how to recognize many targets on the cancer cells, and there would be no need to train them to reach the tumor.
The researchers used advanced techniques to upgrade the tumor-fighting immune cells and teach them to more effectively attack the cancer cells. They were then encouraged to reproduce and re-infused into the patients’ bodies. Such treatment is given only once, and today similar treatments are given only in a few medical centers in the world, including the Sheba Medical Center in Tel Hashomer, as part of experiments in personalized medicine.
The treatment was tested on 168 patients with advanced melanoma, most of whom did not respond to other treatments. Half received the new treatment and the rest received one of the standard treatments currently offered to melanoma patients – the biological drug ipilimumab, marketed under the name Yearboy, which is based on an antibody that binds to the cells of the immune system and helps them damage the cancer cells.
The progression of the disease in half of the recipients of the upgraded immune cells was halted for a little more than seven months, compared to only about three months in half of those who received the standard treatment. 49 percent of the patients who received the experimental treatment responded to it by reducing the metastases, and in 20 percent of the patients they disappeared completely. In the group receiving the standard treatment, the metastases were reduced in only 21 percent of the patients, and disappeared in only seven percent. In addition, the patients with the upgraded cells survived on average longer after treatment compared to the ipilimumab recipients. The new treatment, therefore, achieved significantly better results than the standard treatment. He was able to reduce the tumors better and extend the patients’ lives longer.
All patients with the new drug and almost all recipients of ipilimumab experienced side effects. The side effects of the recipients of the experimental treatment, such as nausea and vomiting, fatigue and a decrease in the number of white blood cells, were mainly due to the short chemotherapy treatment given to them before receiving the drug, with the aim of reducing the amount of normal immune system cells and making room for the improved cells. Despite the unpleasant side effects, most patients reported an improvement in quality of life and function.
Currently, the production of the drug has been handed over to the Netherlands Cancer Institute. The Dutch National Institute of Health is currently examining whether the treatment meets the regulatory requirements for the production of the drug. They will also examine the possibility of incorporating it as a standard treatment in the basic health insurance package offered to Dutch citizens.
A video summarizing the clinical trial in treatment with tumor-infiltrating lymphocytes: