Dr. Martin “Mac” Cheever, a physician-scientist who was a pioneer in the development of lifesaving immunotherapies, is being mourned by friends and colleagues at Fred Hutchinson Cancer Research Center, where he began his career in the earliest days of the Seattle institution.
Cheever died on Sept. 23 from complications following heart surgery. He was 77.
Beloved for his calm demeanor, generosity and wit, the oncologist is respected for his work as one of the first bone marrow transplant physicians at Fred Hutch and for his laboratory studies in the late 1970s that convincingly showed the immune system might be harnessed to stop cancer.
He is also renowned for his years of dedication in building a nationwide system of clinical trials to prove these new therapies are safe and effective for cancer patients.
Throughout his career, Cheever advanced understanding in a new field that eventually led to therapies such as checkpoint inhibitors, which boost the body’s natural immune response to cancer, and CAR T cells, which are immune cells genetically engineered to target tumors.
His work on tumor-related proteins that trigger immune responses also informed ongoing development of cancer vaccines. Although his early research focused on blood cancers, he gradually shifted his emphasis to solid tumors, such as those of the lung, skin, kidney and pancreas.
In 2007, with grants from the National Cancer Institute, he established the Hutch-headquartered Cancer Immunotherapy Trials Network, or CITN, for which he served, until his recent illness, as director and principal investigator. The network brings together academic experts in immunology and helps coordinate and analyze early clinical trials at more than 40 of the top universities and cancer centers in the United States and Canada.
CITN is currently testing 25 potential immunotherapies against a wide variety of cancers in children and adults, helping to gather data that can take potential therapies from experimental stages to widespread use.
Dr. Fred Appelbaum, executive vice president and deputy director of Fred Hutch, said Cheever was his longtime collaborator in clinical research and also a good friend.
"Mac was witty, a little bemused by life. He was very modest about his accomplishments. He had a very pragmatic view and would not get carried away by heated arguments — he was usually a moderating voice,” Appelbaum said.
Cheever came to Seattle as a medical intern and resident at the University of Washington, where he trained as an oncologist and remained a professor throughout his career. His connection to the Hutch began with a research fellowship, and he was appointed an assistant member of the faculty in 1976. Like Appelbaum, he was an early recruit of the Hutch’s Dr. E. Donnall Thomas, who developed bone marrow transplantation as a cure for leukemia. For that work, in 1990 Thomas shared the Nobel Prize in Medicine or Physiology.
A transplant team that included Appelbaum, Cheever, Hutch immunologist Dr. Philip Greenberg and researcher Dr. Alex Fefer formed a tight bond.
"I've had a long, close personal relationship with Mac," Appelbaum said. "When we first moved to Seattle, the Cheevers, Greenbergs and Fefers all became close friends."
He recalls that research by Cheever, Greenberg and Fefer began to draw wide attention in the field in 1977. The three began publishing, with Cheever as lead author, a succession of papers showing that mice with leukemia could be cured by a transfer of white blood cells from another mouse that had developed an immune response to a grafted tumor.
“It demonstrated the ability to transfer tumor immunity from one animal to another,” said Appelbaum, who is holder of the Metcalfe Family/Frederick Appelbaum Endowed Chair in Cancer Research.
He called that early work with mice a big step toward the development of cellular therapies for humans, taking immune cells from the blood of a cancer patients and manipulating them outside the body so they could be returned, with heightened capacity, to wipe out that patient’s tumors.
“Today we have a whole industry of T-cell therapies for tumors,” Appelbaum said.
Cheever has earned numerous honors for his research, including the first ever Distinguished Service Award in 2019 from the International Society for Biologic Therapy of Cancer, which had earlier conferred a Lifetime Achievement Award for team science to Cheever, Greenberg and Fefer.
He was also an entrepreneur, eager to find ways to bring scientific advances from the laboratory to the bedside. In 1994, he left the Hutch to be a cofounder of Seattle biotechnology start-up Corixa Corp. to develop therapeutic cancer vaccines. The company successfully developed Bexxar, an FDA-approved radioimmunotherapy for lymphoma. He remained there as a vice president of clinical research until 2005, when it was acquired by GlaxoSmithKline. Cheever returned to Hutch that year, where his industry-honed expertise in clinical trials design launched him on the path to creating CITN.
“It’s hard to imagine a career in cancer immunotherapy without Mac,” Greenberg said. “We grew up in the lab together, depending on each other to solve different aspects of the larger problem. … I was more of a basic sciences guy, but he was fully committed to making immunotherapies that could be translated to the clinic, something that would help patients. His eye was always on the patient.”
Greenberg added that Cheever’s focus on translating research to benefit patients often guided their work together and the questions they tried to address.
“Mac retained that focus throughout his career, much to the benefit of patients,” he said.
Greenberg noted that Cheever’s friendly, conscientious personality reflected his Michigan roots.
“He was very Midwestern,” Greenberg said. “A gentle soul. He was generous, collaborative and helpful. We worked together for many years, and Mac was a master of being able to disagree without ever being disagreeable.”
Cheever was a backer of environmental causes and an avid electric bike rider. He supported developing the 285-mile Palouse to Cascades Trail and had ridden most of it. He had planned to complete the remaining link to Idaho, south of Spokane, after recovering from surgery.
He is survived by his wife of 49 years, Linda, of Mercer Island, Washington; his sons Alexander, of Mercer Island, and Paul, of Seattle; his brother Carl, of Seattle; and his sister Martha Richardson, of Lincoln, Nebraska.
A memorial celebration of his life for family members and friends is tentatively planned for spring 2022. His family suggests donations in his name be made to Fred Hutch, the Medic One Foundation or the Palouse to Cascades Trail Coalition.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.
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