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Cancer Immunotherapy Named ‘Breakthrough of the Year’

Science lauds ground-breaking treatment (December 20)

The journal Science has cited cancer immunotherapy as the “breakthrough of the year,” although the treatment has worked only in a small number of patients and only in certain cancers, including melanoma and leukemia.

“Oncologists, a grounded-in-reality bunch, say a corner has been turned and we won’t be going back,” the journal remarked.

Immunotherapy’s successes emerged from a careful decoding of basic biology that spanned many years. The early steps were taken by cancer immunologist Dr. James Allison. In 1987, French researchers identified a new protein receptor on the surface of T cells, called cytotoxic T-lymphocyte antigen 4 (CTLA-4). Allison found that CTLA-4 puts the brakes on T cells, preventing them from launching immune attacks. He wondered whether blocking the blocker — the CTLA-4 molecule — would set the immune system free to destroy cancer.

In 1996, Allison published a paper in Science showing that antibodies against CTLA-4 eradicated tumors in mice. Three years later, rights to the antibody were acquired by a small biotechnology company, Medarex, making the leap from biology to drug.

Crucial results didn’t come for another 11 years. In 2010, Bristol-Myers Squibb — which had bought Medarex — reported that patients with metastatic melanoma lived an average of 10 months on the antibody, compared with 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial.

Engineered T cells are still experimental, but the antibodies are slowly going mainstream, Science says. At least five major drug companies are developing antibodies. In 2011, the FDA approved the anti–CTLA-4 treatment ipilimumab (Yervoy, Bristol-Myers Squibb) for metastatic melanoma. The cost is high, however: The company charges $120,000 for a course of therapy.

The journal concludes: “Even in the fluid state oncology now finds itself, this much is certain: One book has closed, and a new one has opened. How it will end is anyone’s guess.”

Source: Science; December 20, 2013.

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