Sheba Doctors: Experimental Treatment Successful in Half of Melanoma Cases

Israeli researchers have found that an experimental skin cancer treatment can reduce some tumors and cause others or disappear entirely, doctors at Sheba Medical Center, Tel Hashomer, wrote in a recent article in the scientific journal Clinical Cancer Research.

The treatment has been tried on melanoma patients who have been told they have only a few months to live because other treatments have failed. It uses the cells from the patients' own immune systems to attack the cancer.

In nearly half the cases in the experiment, the treatment caused the tumor to shrink or disappear entirely. Twenty-nine patients received the treatment over the past two and a half years. Doctors at Sheba's Ella Institute for Treatment and Research of Melanoma and Skin Cancer reported their findings in the May issue of Clinical Cancer Research.

"Melanoma is considered one of the most difficult cancers," said Prof. Jacob Schachter, head of the Ella Institute and deputy director of oncology at Sheba. "At its late stages it metastasizes to many other parts of the body, unlike, for example, cancer of the large intestine, which metastasizes mainly to the liver. In addition, about half of metastatic melanoma patients are young, and their life expectancy is six to eight months on average."

Sheba is the second medical center in the world to implement the treatment, which was developed over the past decade by the National Cancer Institute in Maryland.

The treatment, approved by the Health Ministry and Sheba's committee on human experimentation, was offered only to patients whose cancer had spread and for whom other treatments, including surgery and chemotherapy, had failed.

The treatment involves taking cells from the patients' immune system, known as tumor infiltrating lymphocytes. These cells, which kill cancer cells and are found in cancerous organs, are developed in a laboratory and then returned to the patient's body to attack the cancer.

At the first stage of the treatment, a cancerous organ relatively easy to remove by surgery is removed, and its lymphocytes are isolated. They are then grown for three to four weeks in the laboratory in bags with 40 liters of fluid until there are 1,000 times more than the initial number. A week before the end of the cell-generating process, the patients are given aggressive chemotherapy to suppress their natural immune system, so that the body will easily accept the laboratory-grown cells.

About a week after the chemotherapy, with the patient still hospitalized, the patient is given one infusion of a concentrated dose of the laboratory-generated cells. The patient is also given interleukin-2, which restarts the immune system.

"The cells that are inserted into the body already know the metastases of the cancer, because they came from one of them. They therefore head, like guided missiles, toward the metastases and take it apart," Schachter said.

After the cells of the metastases are destroyed, white blood cells called microphages take apart their remnants and turn them into refuse. The immune system recovers within two to three weeks, when the patient goes home. A month later the patient undergoes a CAT scan to see how the treatment has affected the cancer.

The Sheba team reported that 48 percent of the patients responded to the treatment. Out of 29 patients, three experienced the complete disappearence of the tumor and the metastases a month after treatment. In 11 other cases the response was partial, but the patients are still alive and are now functioning again. The first patient whose metastases disappeared is still alive after more than two years, and the other two are still alive after 16 months and 10 months. Among the patients whose tumors partially shrank, four have been alive for 18, 24, 27 and 16 months, respectively, and report improved quality of life. All patients undergo CAT scans every three months.

In addition to Schachter, the team reporting the findings includes Dr. Michal Besser, head of the Ella Institute laboratory, and Dr. Avi Treves, Ella's scientific director and deputy head of the Sheba Cancer Research Center. The encouraging clinical findings and the eventual simplification of the treatment will have a significant impact on this generation of cellular treatments for cancer, the researchers wrote.

According to cancer statistics collected by the Health Ministry, 1,300 new melanoma cases were diagnosed in 2008, 100 new cases more than in the previous year. Of these, 830 were of the invasive type of melanoma.

Sheba is expected to submit a request to the Health Ministry soon to recognize the treatment as non-experimental in patients with terminal cancer.

The current findings are based on the second generation of experimental treatment, which makes use of cells that have undergone short-term generation in the laboratory and are injected into the patient's body while the cells are still young.

"The less time the cells grow in a laboratory culture, the more aggressive they are in acting against the metastases after being reintroduced to the body," Schachter said.

Sheba is also working on expanding the technology to other types of cancer, including terminal kidney cancer. "Specific methods must be developed for each cancer to grow the immune system's components," Treves said.