James Allison, PhD
The immense impact of immunotherapy is well known to those in the oncology space. Over the last few years, it has become a therapeutic option that more and more patients request, as they have seen the life-changing outcomes it has had on those battling malignancies, such as melanoma and non–small cell lung cancer.
following the announcement of his Nobel Prize, Allison reflected on his research in immunology, the impact it has had on patients with cancer, and where the field is headed.
OncLive: What are the challenges of translating discoveries made in the laboratory to the clinic?
Firstly, just having enough funding to concentrate on fundamental science puts pressure on everyone to actually do translational stuff from the start. The truth is, you are not going to get any major discoveries that way—you have to do the fundamental science and understand the mechanisms. That is where CTLA-4 blockade came from. [We were] not trying to cure cancer, it came from trying to understand the mechanisms of T-cell activation. Once we understood that, I [thought], "This gives me an idea about a new way to treat cancer." I would submit that no one who was just trying to figure out how to use the immune system would have ever found CTLA-4. That is the first thing: to provide more funding for fundamental science, and mechanisms that are potentially important for treating [patients with] cancer. Then, be aware of new discoveries and things that will take you along the way. Both need to be done.
For a few years, I had a hard time finding anyone who would take a chance on what we were trying to do because they did not understand the mechanisms. I think the answer is more science—more hardcore science.
What would you say to the next generation of scientists about the world of immunology and how it has changed, especially in light of the recognition that the Nobel committee has given it?
When I started, I was interested in a subset of immunology, which was T cells. There was nothing known about them except that they cruised all around your body, looked for problems, and fixed them. The mechanisms just fascinated me. How do they do that? How do they recognize it? How do they get turned on and get turned off, and decide what to do?
We still, in my opinion, are only scratching the surface on understanding the complexities of those mechanisms. It used to be that people thought there were these discrete pathways that T cells differentiate along and are stimulated by. Now, we are beginning to see that it is more fluid than that—it is a dynamic process.
If we are going to really use T cells and immunotherapy, we need to understand those sorts of things. We need to understand the impact of epigenetics and the development of different signaling pathways in some detail. Particularly if we are going to start putting these things in combination with genomically-targeted kinase inhibitors, that is a very powerful way to go. We don't know enough about what those things do to the immune system to make any movement there.
It has become clear in the last 3 years or so that immunotherapy is the fourth pillar of cancer therapy. Surgery, radiation, and chemotherapy are pretty much “siloed,” and immunotherapy is unique, as it can work with those other things. What we need to do now is work on a universal way of combining all of these and hope for synergy. If you come in with a checkpoint blockade, you will get T cells that [the patient] will have for the rest of their life—the chemotherapy will be gone in hours.
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