“It’s in many respects a career achievement award. It means that you’ve impacted science. And you get nominated and elected by people whom you really admire and respect, which is a great honor,” Greenberg said. “But these kinds of honors, while given to an individual, reflect something much bigger than what one person did.”
“For that, I’m grateful to all the people who’ve come through my lab and both shared the vision we had and helped realize that vision. More than 40 of those people have gone on to their own independent academic labs, as well as many others into biotech, where they are making amazing contributions. It’s like being part of a big family. This is about what we have accomplished, not what I have accomplished.”
Greenberg is one of 120 new members elected by their peers “in recognition of their distinguished and continuing achievements in original research,” according to the NAS press release.
In the early 1970s, after completing his medical education, Greenberg pursued post-doctoral training in immunology and immunogenetics.
“It was the hot new thing then,” he said. However, its relevance to cancer was in question. “There were people who thought it wouldn’t be relevant at all. As an obstinate New Yorker,” he said, “I believed it would be.”
E. Donnall Thomas, MD, agreed. In 1976, he recruited Greenberg to join Fred Hutch. “At the time,” Greenberg recalled, “this was really the only place in the world linking immunology to human cancer.”
Nearly 50 years on, work by Greenberg and others at Fred Hutch has proved this link was worth pursuing. Greenberg has contributed significantly to understanding the kinds of antigens a T cell can recognize in a tumor and developing technologies to isolate T cells from human peripheral blood and then expand and clone them with retention of specificity. This allowed his lab to probe the unique characteristics of the cells and develop a cell population that could be used first in pre-clinical models and then in humans in which it was possible to track the T cells and investigate what they could and could not do.
Greenberg was involved in some of the first clinical trials to administer genetically modified T cells to people to target and eradicate disease. Most importantly, he said, as technologies have improved he and his team have been able to identify obstacles to T-cell therapy and explore ways to genetically modify T cells to make them more effective, such as ensuring they survive long enough after infusion into a patient to produce a sustained, long-term anti-cancer response.
While his earlier translational work focused on cytomegalovirus in blood and marrow transplant recipients and on human immunodeficiency virus, he has since used antigen-specific T cells therapeutically against numerous types of malignancies, including melanoma, acute myeloid leukemia, ovarian cancer, pancreatic cancer and others. He will launch a set of clinical trials by the end of 2023 and in early 2024 targeting mutations in the KRAS gene, implicated in several cancer types. The approach has shown promise in pre-clinical studies.
“It’s an extraordinarily exciting time for us. The pace at which the science is changing what we know and what can be done is just remarkable,” said Greenberg, who is a professor of immunology and medicine in the division of oncology at University of Washington School of Medicine. He was a founding member of the UW Department of Immunology and the Fred Hutch Program in Immunology.
Established by Congress in 1863, the NAS provides science, engineering and health policy advice to the federal government and other organizations. It has 2,565 active members, including those elected in 2023. Greenberg is the 13th Fred Hutch faculty member elected to the academy.