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Presentation Speech by Professor Klas Kärre, Member of the Nobel Assembly at Karolinska Institutet, Member of the Nobel Committee for Physiology or Medicine, 10 December 2018

Your Majesties, Your Royal Highnesses, Honoured Laureates, Ladies and Gentlemen,

Cancer, one of the greatest scourges of humanity, is caused by the uncontrolled proliferation of diseased cells that can spread in the body and form metastases. Cancer therapy has been based on three pillars: surgery, radiotherapy and drugs that attack cancer cells. Today more than two thirds of cancers are cured, but the disease still claims millions of lives every year. There is a great need for new forms of therapy, and for a long time researchers have pinned their hopes on the possibility of utilising our immune system, which normally protects us against infections.

The immune system is based on a diversified array of instruments, in the form of various cells and molecules. Each of them has its own special sound and technical requirements to get them to work, a bit like the instruments in the orchestra here today.

The fundamental task of the immune system is to distinguish between foreign cells – and react against them – and the body’s own cells, which it must leave in peace.

T cells − a kind of white blood cells that act, among other things, as killer cells − use a special instrument called a receptor to identify cancer cells as foreign. By the 1990s, cancer immunology researchers had shown that T cells will then react, but unfortunately in a much too timid way. Let’s ask the orchestra to illustrate.

Beautiful and clear, but alas – so short, slow and weak! Playing “andante and pianissimo” was not enough to eliminate cancer cells. This year’s Nobel Prize in Physiology or Medicine goes to two researchers who discovered how we can release the brakes that hold back the immune system, thereby mobilising it for cancer therapy. Both Laureates are immunologists, but neither was actually a cancer researcher from the beginning. This story therefore illustrates something important: the unexpected benefits of basic research.

In the mid-1990s, Jim Allison was working in a field of research that identified “gas pedals” that amplified the reaction of T cells, but also a “brake pedal” that weakened it. He tested the very bold idea of releasing the brake pedal by using antibodies to trigger T cell reactions against cancer. He began by curing cancer in mice. Then he worked step by step to develop this therapy for humans. He called it “checkpoint inhibition”. In the first clinical studies of malignant melanoma, some patients responded dramatically – even in patients with the disease all over their bodies, the metastases shrank away and disappeared.

Tasuko Honjo had already discovered a new molecule on T cells in the early 1990s. Through many years of systematic work, he was able to show that it serves as another braking mechanism in the immune system. Inspired by Allison, he showed that blocking this brake also triggered attacks on cancer cells in mice, and that it worked in a new way. Honjo suggested that this might be developed into a powerful cancer therapy. Clinical researchers were later able to confirm his hypotheses: this form of checkpoint inhibition leads to responses in more patients and also works against additional forms of cancer.

The two therapies have especially strong effects when used together. Let’s get a preview by returning to our immune system orchestra. You remember how pathetic it sounded last time. Now let’s hear how the same reaction looks when we release the brakes. Maestro?

Allegro e Fortissimo! That was a bit different, the way it should sound!  By orchestrating the immune system in the right way, it has proved possible to control or eliminate the disease in tens of thousands of patients. Many are still tumour-free after more than five years. This new pillar of cancer therapy is already solid, and the Laureates’ discoveries have inspired a whole new field of research. Like the Carmen Overture, it promises an exciting future.

Professors Allison and Honjo,
Your ground-breaking research has added a new pillar in cancer therapy. It represents a new paradigm for treatment, not directly targeting the cancer cells, but rather releasing the brakes of the immune system. Your seminal discoveries constitute a landmark in the fight against cancer, for the benefit of numerous patients and all humankind.

On behalf of the Nobel Assembly at Karolinska Institutet, I wish to convey to you our warmest congratulations. May I now ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.