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Checkpoint inhibitor scientists win Nobel Prize

Winners Allison and Honjo inspired efforts to eliminate tumour cells efficiently

Nobel Prize

The 2018 Nobel Medicine Prize has been jointly won by James Allison of the University of Texas and Tasuku Honjo of Kyoto University for working out how to mobilise immune cells against cancer.

The award comes as immuno-oncology is starting to transform the way cancers are treated, and fittingly goes to scientists responsible for the first generation of T cell-boosting checkpoint inhibitor drugs that have spearheaded what has become the fastest-growing area of oncology.

Honjo was instrumental in discovering the role of PD-1 – targeted by an expanding array of drugs including Merck & Co’s Keytruda and Bristol-Myers Squibb’s Opdivo – while Allison was at the heart of research into CTLA4 which led to the development of inhibitors such as BMS’ Yervoy (ipilimumab) and various late-stage clinical candidates.

“By stimulating the inherent ability of our immune system to attack tumour cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy,” said the Nobel Assembly at Karolinska Institute in a statement. “Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer.”

Allison was working on CTLA4 at the University of California, Berkeley, during the 1990s when much of the research on it was directed at ways to treat autoimmune disease. He followed a different path, developing an inhibitor that shrank tumours in mice and was eventually licensed to small US biotech Medarex – which was bought by BMS in 2009. Two years later the antibody – now called Yervoy – was approved by the FDA for melanoma after extending survival in late-stage testing.

Honjo’s work was also carried out largely in the 1990s, and showed that PD-1, like CTLA4, functions as a T-cell brake, but operates by a different mechanism. That paved the way for using PD-1 as a target in the treatment of patients, with studies showing long-term remission and possible cure in several patients with metastatic cancer, and led to the approval of Opdivo in Japan in 2014 as the first drug in the class.

With new drugs targeting the PD-1 and CTLA4 pathways no reaching the market – and research intensifying on other checkpoint inhibitors – “Allison and Honjo have inspired efforts to combine different strategies to release the brakes on the immune system with the aim of eliminating tumour cells even more efficiently, says the Nobel Assembly.

Allison, who is executive director of the immunotherapy unit at Texas’ MD Anderson Cancer Center, said: “I’m honoured and humbled to receive this prestigious recognition.”

“A driving motivation for scientists is simply to push the frontiers of knowledge. I didn’t set out to study cancer, but to understand the biology of T cells – these incredible cells travel to our bodies and work to protect us.”

Meanwhile, Honjo told a news conference reported by the Japan Times that he was “very honoured and pleased to receive the Nobel Prize in physiology or medicine”, and would “like to continue the study a bit more so that this immunotherapy can further assist cancer patients in the future.”

Article by
Phil Taylor

2nd October 2018

From: Healthcare



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