New Hope for Advanced Melanoma Patients

Anti-tumor T cells fight skin cancer

(RxWiki News) White blood cells are the good guys, the soldiers of our immune system. They fight off disease, including cancer. But even when these cells have been specially trained to attack tumors, they haven't survived long enough to do any good against crafty, nasty melanoma cancer cells.

Scientists have changed that. Cancer-fighting white blood cells now have a fighting chance against melanoma (skin cancer) thanks to a new technique discovered by scientists at the Dana-Farber Cancer Institute.

Researchers have found a technique to inject specially fortified cells - known as anti-tumor T cells - that can survive longer in the body so they can fight the good fight, without the use of additional treatments that often have harsh side effects.

"New technique boosts immune system's power in killing off cancer cells."

In a paper published in Science Translational Medicine, the researchers report the results of a small, Phase I study in which the technique -- a form of "adoptive immunotherapy" -- was tested in nine patients with advanced melanoma.

Lead author, Marcus Butler, MD, of Dana-Farber's Early Drug Development Center, says of the discovery, "Our technique opens the way to therapies that produce less-toxic, long-lasting immune system attacks on cancer cells."

When combined with another treatment, the technique showed even great promise. Five patients whose disease had progressed after T cell infusions were treated with a drug that boosts the cells’ anti-tumor response.

Three of the patients had long-term shrinkage of their tumors, and two others had their disease stabilize. Patients who received the drug after completing the clinical trial had sizable increases in the number of anti-tumor T cells in their blood.

Researchers found that patients with the highest post-treatment levels of anti-tumor T cells did not necessarily fare better than those with lower levels. This wasn't surprising, researchers say, because many tumors have developed an ability to defend themselves against a T cell attack.

This was a Phase I study designed to test the safety of this technique. Researchers report that additional study is needed to perfect the technique.

Melanoma skin cancers were diagnosed in more than 68,000 Americans in 2010, according to the American Cancer Society, and the numbers have been rising for more than 30 years. If detected and removed at an early stage, melanomas can usually be cured, but once the disease has spread to distant sites, the median survival time for patients is less than a year.

Scientists are developing an array of novel treatment approaches to improve those odds.

In Depth

  • Adoptive immunotherapy involves collecting T cells - natural infection and cancer-fighters of the immune system -- from a patient and exposing them to protein "antigens" found only on tumor cells
  • The T cells learn to recognize the antigens and to attack tumor cells that carry them
  • Technicians treat these "educated" T cells with a growth stimulator to increase their number and then inject them back into the patient, where they fan out to killtumor cells
  • Under normal conditions, the reinjected T cells die off in a matter of days
  • Doctors can increase their staying power by depleting patients’ blood of certain regulatory T cells that dampen the anti-tumor T cells' response to cancer or using Interleukin 2, which spurs the growth of T cells.
  • Both techniques can cause a host of health problems, including nausea, fever, muscle weakness, a drop in certain kinds of white blood cells, as well as other, more severe ones
  • The technique developed at Dana-Farber aims to reduce those problems while giving anti-tumor T cells the stamina to persevere in the body
  • It involves an artificial version of cells known as antigen-presenting cells which inform the immune system that cancer is present and needs to be eliminated
  • Dana-Farber scientists engineered antigen-presenting cells to produce a key molecule, known as CD83, which ensures that T cells persist for a long period of time
  • They also used Interleukin 15 to educate the T cells to be survivors
  • These educated T cells, known as memory cells, use their “knowledge” of tumor antigens to prepare them to launch a swift, powerful attack on tumor cells
Review Date: 
April 26, 2011