For more than 40 years, Dr. Phil Greenberg has been working toward a vision: harnessing the power of a patient’s immune system to safely and effectively kill their tumors. When the Fred Hutchinson Cancer Research Center scientist started his career, the idea was far from mainstream. Now, there’s a Nobel Prize, immunotherapies have become standard of care for several cancers, and a constant flood of new approaches are pouring into clinical trials.
Greenberg is one of the scientists who made that revolution possible.
Years before cancer immunotherapy started showing up on the nightly news, his team provided a bevy of “firsts” that demonstrated the power of immune cells called T cells to target and eradicate disease. Today, their latest innovations are offering new hope in some of the toughest cancers.
In recognition of his expertise and ongoing impact on the field, Greenberg will receive the 2018 Richard V. Smalley, M.D., Memorial Award and Lecture, the highest honor granted by the Society for the Immunotherapy of Cancer. The organization will grant the award on Saturday in Washington, D.C. at its annual conference.
We caught up with Greenberg before he left for the meeting, asking him five questions about where cancer immunotherapy is now and what is coming on the horizon. The transcript below has been lightly edited for readability.
What should current cancer patients know about where the immunotherapy field is now and where it’s going?
The strategies that have been evolving for immunotherapy have now shown unequivocal benefit — and sometimes remarkably dramatic responses and even tumor eradication in a substantial fraction of patients. Whether an immunotherapy is a therapeutic option is a reasonable discussion to be having now for many, many cancers.
With that said, we still don’t have strategies that we can demonstrate are effective at treating a large number of cancers. So it is an evolving field. We need to recognize that this is a field in its infancy now, and we’re just learning how to make it better.
But there’s no question that this is all going to improve: that the efficacy in the diseases that are responding now will get better, and the breadth of diseases that can be treated with immunotherapy will increase. So it’s a very exciting time in the field.
What are you most excited about in your own lab?
Our lab is mostly focused on a strategy involving what’s called synthetic biology: engineering T cells to target malignancies. This really reflects the fact that strategies being pursued to augment our own immune system are going to work in some settings, but there are many settings where our own immune system is not working, or not going to work efficiently enough to get rid of cancers. So we’ve been developing strategies to genetically engineer a patient’s immune system so that it’s actually programmed not only to recognize but also to more effectively function in the context of a tumor.
We’re very excited about some of our results now in treating acute myelogenous leukemia, and we are looking forward to starting in 2019 a trial targeting pancreatic cancer with an engineered T cell and probably shortly thereafter a trial in ovarian cancer, as well.
Earlier this year, we asked you for a prediction about 2018, and you said:
“2018 should be a watershed year for therapy of cancer with engineered T cells. The breadth of malignancies that can be targeted with T cells will increase, and the use of existing and developing technologies to enhance the activity of these T cells will make this therapy increasingly useful and effective.”
Has that prediction come true?
I would say that that still remains accurate, but we’re certainly not where we want to be right now. …
Each time we develop a new strategy, we learn not just why it's successful in some patients, but also why in some patients it’s not successful. Fortunately, the technologies now exist to probe the depths of the results in individual patients so we can understand that. And the technologies also exist now to change the way we engineer cells so they can overcome that.
So, again, I think one really does need to recognize that we’re just at the beginning of this. And I think it’s absolutely certain that these are all going to be strategies that get better.
I often hear experts highlight the need for combination immunotherapies. How is the field approaching the question of combining different immunotherapies?
Increasingly, investigators in the field have been able to understand why we’re not getting success in some studies, or why success is limited in some studies.
One obstacle is the tumor microenvironment, which is essentially the cells and the structures that surround a progressing tumor. So combinations are really going be a question of: How do we change the environment that surrounds the tumors so that it is more hospitable to an effective immune response and less obstructive to an immune response?
We’re learning how to modulate that [tumor microenvironment]. We can modulate it using agents that go into the tumor microenvironment and change it. Or by engineering T cells so that when they get to the tumor microenvironment they can function and they can change the microenvironment by what they produce.
You’re in the thick of things in the lab, you’re excited about what’s coming up. But eventually, you may start to think about retiring — not that that’s going to come anytime soon! Where do you hope immunotherapy will be at that point?
Yeah, it’s such an exciting field now that it’s just not one that I can see myself retiring from. At least not in the immediate future.
But I do want to see us having established an [immune] therapy that would become standard of care for acute myelogenous leukemia, and I think we’re getting close to that. And I want to see us at least on the way to establishing a therapy that benefits the majority of patients with pancreatic cancer and patients with ovarian cancer. And I believe that those are all targetable strategies.
I hope to work with Aude [Hutch faculty member Dr. Aude Chapuis, a former Greenberg trainee] to develop strategies that will make Merkel cell carcinoma [a rare skin cancer] a responsive disease. And it also looks like we’re going to be reaching toward trying to treat lung cancer and myeloma, as well.
I think it’s so difficult now because we can see so many opportunities. Just trying to have the resources to be able to realize some of those visions is actually part of the problem right now. But all of these [opportunities] are reachable now. So it’s both an exciting and frustrating time.
Susan Keown was a staff editor and writer at Fred Hutchinson Cancer Center from 2014-2022 who has written about health and research topics for a variety of research institutions. Find her on Twitter @sejkeown.