Armed Against Cancer

By Medical Discovery News

March 3, 2012

Armed Against Cancer

Imagine if a patient’s own cells could fight cancer rather than struggle through chemotherapy and radiation. For two decades scientists have attempted to do that with T-cells, but no one came close until the remarkable success of a pilot study at the University of Pennsylvania.

Two out of the three leukemia patients they treated remained cancer free a year after nearly dying. And the third is in partial remission.

The researchers, led by Dr. Carl June, were able to accomplish three things that hadn’t been done together before: engineer T-cells to fight and kill leukemia cells, have them multiply when inside the body, and then diminish and leave a set of memory T-cells to multiply again and kill leukemia cells if they show up later.

The results stunned even the researchers involved, whose intentions were only to test the therapy’s safety. First, they extracted T-cells, a type of immune cell, from the patient and supplied them with a gene that creates something called a chimeric antigen receptor, or CAR, on the surface of T-cells. This new receptor, CAR, is supposed to recognize and kill B-lymphocytes, which grow out of control in a chronic form of adult leukemia.

But in past clinical trials, when these CAR T-cells were transfused in the patient, they failed and died without doing much damage to tumor cells. In this newest study, however, researchers added an extra gene to the T cells called 4-1BB.

The 4-1BB encoded protein enhances the cell’s tumor-killing ability, and instructs CAR T-cells to multiply and persist as memory cells. But its response isn’t so severe that it kills the patient, which has happened in other CAR T-cell trials.

The fascinating part of this study is researchers used a disarmed HIV, the virus that causes AIDS, to deliver these cancer-fighting genes into the patient’s T-cells. Even though the thought of injecting HIV may be unsettling to most people, this disarmed virus isn’t harmful and does not multiply in the body. The choice makes sense because HIV naturally targets and penetrates T-cells.

A few weeks after transfusing these engineered T-cells in patients, doctors could find no cancer cells anywhere. The researchers estimate more than two pounds of leukemic cells were destroyed. As for the third patient, researchers think it’s possible his steroid treatments may explain why he ended up in partial remission.

June’s team is now planning wider clinical trials to include more patients. The aim will be to test the efficacy of the therapy and its adverse effects. For example, one of the targets on the tumor cell is also found on healthy membranes that line the chest and abdomen.

Researchers are optimistic that this therapy can treat not only leukemia, but other serious cancers such as those of the ovaries, pancreas and mesothelioma, a cancer of the tissue that lines most major organs. Scientists believe this study marks a turning point in gene therapy against cancer, and future studies will use its novel approaches to develop life-saving treatments.

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