James Allison, Tasuku Honjo win Nobel for CTLA-4/PD-1 discoveries

James Allison and Tasuku Honjo. (MD Anderson/Kyoto University)

James Allison and Tasuku Honjo have jointly received the Nobel Prize in physiology or medicine for their work on immune checkpoints. Allison and Honjo set the stage in the 1990s for the current immuno-oncology boom by discovering the cancer-killing potential of CTLA-4 and PD-1, respectively.

The Nobel assembly honored Allison for work that led to the development of Bristol-Myers Squibb’s immuno-oncology drug Yervoy. Specifically, Allison played a big role in uncovering the anticancer potential of CTLA-4, the target of Yervoy. Working with postdoc Dana Leach, Allison showed in 1996 that injecting anti-CTLA-4 antibodies into mice eradicated colorectal carcinoma tumors.

In parallel, Honjo was working on PD-1. Honjo discovered the protein on the surface of T cells in 1992 and set about trying to figure out its function. Researchers, including Honjo, showed that PD-1 played a role in a tumor escape mechanism. And in 2005, Honjo co-authored a paper describing the effect of PD-1 blockade on the spread of melanoma and colon cancer cells in mice.

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While the idea that the immune system plays a role in controlling cancer dates back more than 100 years, the work of Allison, Honjo and other researchers who studied CTLA-4 and PD-1 over the past few decades validated the concept and turned it into an effective therapeutic approach. The result is dramatically improved outcomes for some cancer patients and an explosion of research into ways to build on progress made to date. 

As is typical for Nobel prizes, the focus on individuals overlooks the important roles played by other people. To take CTLA-4 as an example, Allison's work was part of a sequence of advances starting before Ron Schwartz and Marc Jenkins’ work on costimulatory signals and running beyond Nils Lonberg’s involvement in the development of the ipilimumab molecule.