We Know Immunotherapy Works, But We Need To Find Out Why It Doesn't, Too
THE WEEK|May 02, 2021
INTERVIEW
Namita Kohli

What changed for you after the Nobel?

After the Nobel, several things changed for me. There came a sudden, not necessarily wanted, notoriety [laughs]. I couldn't go to a grocery store without people seeing me. I couldn't just be a person, you know. For a couple of months, my ability to work was affected because people would come up and see me. But it did all come back to normal, eventually.

The positive thing that really happened was the fact that immunotherapy, which was so controversial for so many years—for long, it was considered 'voodoo', 'quack medicine'—[got recognised]. I didn't really get into the big argument for a long time, because to me it made sense to focus on my work and see how it really came out. We know now that it works. We know that a lot of people with cancer are getting cured now, and so, having it finally accepted as a way of treating cancers, that is really a positive thing. Now, I can actually sit down and have discussions with people who were like ‘you have to identify the causes of cancer and block the mutations instead of saying that we make the immune system work’.

Besides the Nobel, the thing that really consolidated the whole result (of Allison's work on immunotherapy) was that the American Cancer Society released data saying that the mortality rate due to melanoma had fallen by 18 per cent, and this has largely been due to immunotherapy. It has made a difference in people's lives, and as a scientist, as someone who mostly wants to figure out how things work, being able to do something that helps people... that has been really great.

It has worked for other cancers beyond melanoma, too.

Yes, the checkpoint blockade—CTLA4 or PD-1 (that came afterwards; they keep the body’s immune response in check)—have been approved now for several cancers besides melanoma, including lung cancer, head and neck cancers, kidney and bladder cancer, cancers of lymphoma, and on and on…. There are about 30 different kinds of cancers. The response rates are 25-40 per cent… so we have got a lot of work to do. We know it works, but we need to find out why it doesn't, too. We are still doing our lab work on that, trying to see what's missing in the cancers that don't respond better [to immunotherapy]… what makes it different from people who respond better…. The goal now is to get us close to 100 per cent [smiles].

The good news in melanoma is that it is close to 60 per cent now; 55 per cent or so with a combination of CTLA-4 and PD-1 together. The five years of survival so far in a trial stands at 55 per cent. There is no reason why that wouldn't continue for ten years. If we just work hard, I don't see why we cannot get it over 55 per cent.

For a therapy that has offered tremendous hope for cancer patients, how has the response from them been?

There have been so many stories... so many letters that I have gotten from people, saying 'thank you, my wife was dying and was in hospice… and she got these drugs, and now, five years later, she's fine'. The most touching story is of Sharon Belvin, the first patient I met. In 2004, she was 22… and dying from metastatic melanoma. She had 31 metastases in her lungs, she had subcutaneous things on her skin, a half centimetre tumour in her brain. Sharon had failed every other therapy. But after she enrolled in one of the early trials, the tumour just went away! I hadn't seen her, but one day, her physician called and asked me to come down to his office. I said, ‘Why, I am busy.’ But he said, ‘No, no... come.’ He was with Sharon and her husband. Here was a woman who had been diagnosed with this disease when she had finished college, had just got married and started on with her life. Now, she has two kids. She has been in therapy for 16 years now. But her recovery was remarkable: the pathologist who was looking at her CT-scans was really amazed. He said, ‘Has there been some kind of mix up? Is this the wrong patient?’…. Over the years, I have seen [Sharon’s] kids grow up…. We have become friends now. It has been great.

What would you recall as your most challenging experience in the journey?

The question about the most challenging experience is an interesting one because science presents you with challenges all the time. You have to figure something out and know that you are right. If you have a sound belief that there are such things as facts, which is not necessarily universally felt these days, you could test them and come up with these ideas…. My work was designed to figure out how the immune system worked, not to discover a cure for cancer. But when we found this negative checkpoint, I had the idea that [if] we blocked it, that could cure cancer. We did the experiments and we could cure almost anything in mice….

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