An interview with Nobel Prize-winning cancer immunologist Jim Allison
Some call it "The Academy Awards Washington," the day when accomplishments are honored not in film, but in the sciences. Earlier this month, the 2018 Nobel Prize winners came to Washington to discuss the work that earned them their field's highest honor.
Among the American winners was Jim Allison, the MD Anderson Cancer Center immunologist best known for his research in cancer immunotherapy. Allison investigated the role played by CTLA-4 in inhibiting the immune response to cancer. He shares this year's Nobel Prize for Medicine with Tasuko Honjo of Japan, who researched the importance of PD-1.
Their findings underpinned translational research that led to the development and approval of the checkpoint inhibitors currently reshaping oncology.
After a symposium, Allison spoke with BioPharma Dive about his work and what challenges lie ahead for immunotherapy.
The following interview has been lightly edited and condensed for clarity.
BIOPHARMA DIVE: Should immunotherapy be offered in combination with other treatments?
JIM ALLISON: Absolutely. When we were first working on it in early animal models, some cancers just melted away but others wouldn't. That was frustrating, so we just started adding stuff. Radiation was good, chemotherapy and vaccines: Almost anything that gets tumor antigens going. We want to kill enough to activate the immune system. We use chemo and radiation to help us vaccinate, not to cure the disease.
What research is being done on late-onset side effects of immunotherapy? Some patients report severe chills, for example.
ALLISON: The bottom line is that for about one third of patients there aren't any that amount to anything. For the rest, there are. People say the effects are auto-immune, but I think they are generally not, they are inflammatory reactions, types of "-itises": colitis, uveitis, hepatitis — it's inflammation run amok.
They can be treated with immunosuppressants given for the short term for symptomatic relief; you wean them off the drugs, and [the symptoms] may never come back. Other people develop arthritis and even diabetes, but it is pretty rare. There are some serious ones, but there's quite a bit of research going on. I had one woman come up to me after a lecture recently — she had pancreatic cancer — and say, 'I don't know whether to kiss you or kick you in the balls.'
Do you have any idea when there could be some promising results for pancreatic cancer?
ALLISON: I would hate to promise. They are working on it very hard. Pancreatic cancer has a lot of macrophages in it, more than T cells, so they could be immunosuppressants. The trick there is to find the right combinations of things to get rid of or change. It's going to take combinations of things, for sure. Pancreatic cancer is a hard one.
Are there promising mechanisms for immunotherapy outside of PD-1 and CTLA-4 inhibition?
ALLISON: There are some more checkpoints, but I think those are the two biggies. Having said that, in melanoma right now, we are up to a 60% [response rate], which is pretty good. Why not 100%? Assuming they don't add toxicity, we may be able to add a third or fourth or fifth, maybe going up to half a dozen drugs. It all depends on the toxicity. And I think at this point, it's going to become individualized.
For example, some of the additional molecules that we've found are in prostate cancer but not melanoma. We are going to start tailoring down the road.
What do see as the ideal balance of power between pharmaceutical companies and independent cancer research?
ALLISON: Both are indispensable. To give you an example from my own work, I started working on T cells in 1982, and I told myself, "I bet this is going to be a great way to treat cancer."
No drug company would have done that. I had to figure out how to get it to work. Translational science is important, but they aren't going to come read the tea leaves. That's what the academic science is for. We don't have to jump around all the time chasing fads.