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For more than 40 years, Dr. Phil Greenberg has been striving to realize a vision: harnessing the power of a patient's immune system to kill tumors safely and effectively. When the scientist at the Fred Hutchinson Cancer Research Center began his career, the idea was far from being adopted. Now, there is a Nobel Prize, immunotherapies have become the standard of treatment for many cancers and new approaches are proliferating in clinical trials.
Greenberg is one of the scientists who made this revolution possible.
Years before cancer immunotherapy began to appear on the evening news, his team provided a host of "firsts" that demonstrated the power of immune cells called T cells to target and eradicate the disease. Today, their latest innovations offer new hope in some of the toughest cancers.
In recognition of his expertise and ongoing impact on the ground, Greenberg will receive the Richard V. Smalley Memorial Award and Conference, MD 2018, the Society's highest honor for cancer immunotherapy. The organization will award this award Saturday in Washington, DC, at its annual conference.
We met with Greenberg before he left for the meeting, asking him five questions about the current impact of cancer immunotherapy and the prospects for the future. The transcript below has been slightly modified for more readability.
What patients with cancer should know about the field of immunotherapy and its evolution?
Strategies that have evolved for immunotherapy have now shown an unequivocal benefit – and sometimes remarkably dramatic responses and even eradication of the tumor in a substantial fraction of patients. The question of whether immunotherapy is a therapeutic option is a reasonable discussion for many cancers.
That said, we still do not have strategies demonstrating that we are effective at treating a large number of cancers. It is therefore an evolving field. We must recognize that this is an area that is in its infancy now and we are learning to make it better.
But there is no doubt that all this will improve: the effectiveness of the diseases that respond now will improve, and the magnitude of diseases that can be treated by immunotherapy will increase. So it's a very exciting time on the ground.
What excites you most in your own laboratory?
Our laboratory is mainly focused on a strategy that uses synthetic biology: T-cell engineering to target malignant tumors. This reflects the fact that the strategies implemented to strengthen our immune system will work in certain contexts, but there are many contexts in which our immune system does not work or does not work effectively enough to get rid of cancer. We have therefore developed genetic engineering strategies of the patient's immune system so that it is actually programmed not only to recognize, but also to function more effectively in the context of a tumor.
We are very excited about some of our current results in the treatment of acute myeloid leukemia and hope to begin in 2019 a trial targeting pancreatic cancer with an artificial T cell and possibly soon an ovarian cancer test. .
Earlier this year, we asked you for a 2018 Forecastand you said: "2018 should be a pivotal year for cancer therapy with modified T cells. The extent of malignant tumors that can be targeted by 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 this prediction become reality?
I would say that is always correct, but we are certainly not what we want to be at the moment. …
Whenever we develop a new strategy, we learn not only why it succeeds in some patients, but also why it fails in some patients. Fortunately, there are now technologies for probing the depth of results in each patient so that we can understand that. And technologies also exist to change the way we design cells so that they can overcome that.
So, again, I think we have to really recognize that we are only at the beginning of this. And I think it's absolutely certain that all these strategies will improve.
I often hear experts stress the need for combined immunotherapies. How does the field address the issue of combining different immunotherapies?
Field investigators have increasingly been able to understand why some studies are not working well, or why their success is limited.
An obstacle is the microenvironment of the tumor, which consists essentially of the cells and structures surrounding a growing tumor. So the combinations will really be a question of: How can we change the environment surrounding tumors so that it is more hospitable for an effective immune response and less obstructive for an immune response?
We learn to modulate this [tumor microenvironment]. We can modulate it by using agents that enter and alter the tumor microenvironment. Or by using T cells so that they can function when they reach the tumor microenvironment and they can modify the microenvironment according to what they produce.
You are at the heart of the team, you are excited about what will happen. But finally, you can start thinking about retiring – even if it will not happen soon! Where do you hope immunotherapy is at this stage?
Yeah, it's such an exciting field now that it's not an area where I would not see myself retiring. At least not in the immediate future.
But I want to see us have established a [immune] treatment that would become the standard of treatment for acute myeloid leukemia, and I think we are getting closer to it. And I want to at least see us on the way to put in place a therapy that will benefit the majority of pancreatic cancer patients and ovarian cancer patients. And I believe these are all targetable strategies.
I hope to work with Aude [Hutch faculty member Dr. Aude Chapuis, a former Greenberg trainee] develop strategies that will make Merkel cell carcinoma [a rare skin cancer] a sensitive disease. And it also seems that we will try to treat lung cancer and myeloma.
I think it's so difficult now because we can see a lot of opportunities. Trying to have the resources to do some of these visions is currently part of the problem. But all these [opportunities] are accessible now. So it's both exciting and frustrating.
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