U.S. immunologist James P. Allison, who recently received the prestigious Wolf Prize in medicine in Jerusalem, has experienced the scourge of cancer first-hand. His mother died of lymphoma when he was 10.
“I was with her when she died,” he recalled. “She had these burns on her neck from the radiation therapy.”
His uncle died of lung cancer, he added, and said his childhood experiences with the disease had made a deep impression on him.
During an interview in Tel Aviv, Allison, 68, a thoughtful, soft-spoken professor of immunology at the University of Texas MD Anderson Cancer Center in Houston, spoke about how he became a pioneer in cancer immunotherapy.
While studying microbiology at the University of Texas, he became very interested in immunology. “At the time I didn’t think, hey, I’m going a discover a cure for cancer,” he said, but he kept the thought in the back of his mind nevertheless.
During his research on T-cells – white blood cells that are the immune system’s attack cells – he found a mechanism that can unleash them to destroy a tumour, rather than poisoning it or killing it with radiation. This led to the development of what is known as immune checkpoint blockade therapy.
T-cells are able to recognize and kill foreign substances such as viruses and bacteria, and also, to a certain degree, cancer cells, which are harder to recognize because they’re not foreign. Allison’s team discovered that a component of T-cells, the CD28 molecule, has to be activated to launch an immune response, however.
“It’s like a gas pedal,” Allison said. “Then the T-cells rapidly multiply and acquire the ability to kill things.”
Allison also found that there are molecules that brake the immune response: CTLA-4 and PD-1. They serve as checkpoints, as it were, to ensure that the immune system doesn’t mistakenly attack healthy “self” tissue. In immune checkpoint blockade therapy, these checkpoints are blocked, enabling the T-cells to remain active longer – but at an increased risk of side effects.
The therapy has been particularly successful in cases of melanoma, the deadliest type of skin cancer. The CTLA-4-blocking antibody ipilimumab, which Allison co-developed, went on the U.S. market in 2011. A PD-1 inhibitor followed.
Initial trials had a success rate of about 20 per cent, and even 60 per cent was later reached with combination therapies, Allison said. Immune checkpoint blockade therapy is now being used for malignancies other than melanoma, too, with varying rates of success.
Allison recalled the dramatic story of a woman with metastatic melanoma – typically a death sentence – who volunteered in desperation for an ipilimumab trial long before the drug had been approved. “In 2001 she received a single injection of the drug, and she’s still alive – 16 years later,” Allison said.
The jury panel of the 2017 Wolf Prize in medicine, which carries a prize of 100,000 dollars, said it had unanimously decided to award it to Allison for “sparking a revolution in cancer therapy through (his) discovery of immune checkpoint blockade.”