'We're ready to take off'

Mac Cheever pilots program poised to lead the nation in translational research for breast, prostate, colorectal and other solid-tumor cancers
Dr. Martin (Mac) Cheever
Dr. Martin (Mac) Cheever, a Hutchinson Center veteran with nine years' experience in the pharmaceutical industry, is back as director of solid-tumor research. The program will provide unique treatment options that stem from breakthrough discoveries at the Center and University of Washington. Photo by Gordon Todd

In the summer of 1971, Dr. Martin Cheever was finishing up his internship at the University of Washington School of Medicine, with plans to apply for a medical-oncology fellowship that fall at Memorial Sloan-Kettering Cancer Center. During the final month of his internship, Cheever had the opportunity to work alongside Dr. E. Donnall Thomas, one of the Hutchinson Center's founding members, who was pioneering the use of an experimental treatment called bone-marrow transplantation as a cure for leukemia and other blood diseases.

Cheever helped Thomas care for the seventh patient to receive such a transplant in Seattle, a teenage boy suffering from aplastic anemia. The disease prevents the bone marrow from producing blood cells — and, at the time, it had no known cure.

"The boy was never expected to survive," said Cheever, known as "Mac" to his friends and colleagues. "But a few months later, his biggest problem was figuring out what he wanted to be when he grew up. I thought to myself, 'this is pretty good stuff'— and I decided to stick around and do my fellowship in Seattle instead."

The transplant procedure that shifted Cheever's career plans would prove to be one of the most significant advances ever developed for cancer treatment, putting the Hutchinson Center on the map as the world leader for treatment of once-fatal blood cancers and earning Thomas a Nobel Prize.

Today, three decades after beginning his own highly successful career in academia and industry, Cheever is back at the Center as director of solid-tumor research, where he plays a key role in the next phase in the institution's evolution. This time, his job is to establish — in conjunction with the Center's research and patient — care partner UW Medicine — of one of the nation's top programs devoted to developing breakthrough treatments for breast, prostate, colorectal and other types of solid-tumor cancers.

"All the essential elements are in place," said Cheever, who, in addition to his position at the Center, is a professor of medicine and associate director of medical oncology at UW. "We have recruited outstanding clinical faculty with expertise in a number of different solid-tumor cancers. We have excellent laboratory investigators who are developing promising innovative approaches for cancer treatment. And with the creation of the Seattle Cancer Care Alliance as our patient-care clinic, we have established much of the important infrastructure needed to expand the number of consequential clinical trials of new and important therapies we can offer to cancer patients. We're ready to take off."

Cheever believes the program has the potential to be a premier destination for patients seeking treatment for all types of cancer with cutting-edge therapies that are developed with the help of the laboratories next door. Such success has long been the case for the Hutchinson Center's bone-marrow transplant program, which attracts patients from around the world seeking treatment with the most promising therapies available — in many cases, administered by the very physician-researchers who helped to discover them.

"Our main mission should be to provide treatment options for patients that are not available elsewhere because they are developed from the unique science at the Hutchinson Center and the UW," Cheever said. "There are a number of areas — such as immune-based therapy and imaging — in which we have arguably the world's top scientific programs and therefore the potential to offer cancer patients unique therapies based on these areas of research."

One of Cheever's top priorities will be to facilitate the movement of unique Hutchinson Center and UW science out of the laboratory and into the clinic, where it will be made available to cancer patients enrolled in clinical trials — a process that is known as translational research, said Dr. Fred Appelbaum, director of the Clinical Research Division and the executive director and president of the SCCA. Among the most promising treatments being developed at the Center are those collectively known as immunotherapy. The approach is based on harnessing the innate cancer-fighting properties of the immune system through antibodies, disease-fighting T-cells and — Cheever's own area of expertise — cancer vaccines.

Experience, leadership qualities

"Mac has a unique set of skills," Appelbaum said. "He comes from a long and very successful career as a researcher who really understands laboratory-based investigations, and he has mentored a number of individuals who have successfully translated their laboratory work into the clinic. Second, he understands the systems at the Hutchinson Center and at UW and therefore, he has hit the ground running. Mac also spent nine years in the pharmaceutical industry, experience that will be invaluable because we will need to work with industry partners to develop some of our research discoveries into therapeutic products. Lastly, Mac has the people skills, insight and leadership qualities that enable him to be successful in tackling great challenges."

Cheever is internationally recognized for his contributions to cancer immunotherapy. The approach grew from the bone-marrow transplantation studies initiated by Thomas and colleagues, who realized the curative potential of the procedure derived from tumor-fighting immune cells, or T-cells, produced by the donor bone marrow. Intrigued by these early findings, Cheever trained with Dr. Alex Fefer and collaborated closely with Dr. Phil Greenberg. Both hold appointments at UW and the Hutchinson Center. In the 1970s and 1980s, the group made a number of the seminal contributions to the field of T-cell therapy before embarking on more independent careers.

Immunotherapy and imaging

As a faculty member of the Center and UW from 1976 to 1997, Cheever worked on developing the principles of T-cell therapy, discovery of potential targets for cancer immunotherapy and development of cancer vaccines. In 1997, he left academia to become a co-founder of Corixa Corporation, a Seattle biotechnology company acquired last year by GlaxoSmithKline. At Corxia, Cheever oversaw the development of three cancer vaccines designed to prevent the recurrence of cancer in patients after treatment — two of which GlaxoSmithKline has already entered into clinical trials and the other is poised to do so. He also had substantial involvement in obtaining Federal Drug Administration commercial approval of Bexxar, a radioactively labeled antibody used for the therapy of lymphoma that was developed in part by Dr. Oliver Press, an investigator at the Center and UW. More recently, Cheever has served as a consultant to the National Cancer Institute's divisions of Cancer Biology and Cancer Therapy and Diagnosis, providing guidance on the how the institute can better facilitate academic immunotherapy research on a national level.

In addition to immunotherapy, biological imaging — in which techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning are used to visualize detailed structures and molecular processes inside the body — is another area that offers the possibility of unique clinical trials, Cheever said.

"The imaging program at UW is the very best in its field. Some of their innovative and highly sensitive imaging techniques allow us to specifically examine how a cancer drug or other therapy is working in the body in a matter of days rather than in weeks or months," he said. "This is an enormous leap in our ability to monitor the effectiveness of cancer therapy and should provide the tools to more rapidly develop new cancer drugs and therapy combinations."

Cheever noted that the solid-tumor clinical trials program will also benefit greatly from another major initiative at the Center: the focus on the discovery of proteins in the blood, called biomarkers, that signify the risk, early onset or relapse of cancer. Such biomarkers may allow doctors to diagnose cancer at its earliest, most curable stages. "Any marker for early diagnosis is potentially a marker that will help us understand the biology of human cancer and that may allow us to precisely monitor the effects of a therapy being evaluated in a clinical trial," Cheever said.

In addition to facilitating greater interaction between laboratory and clinical researchers, Cheever will also act as a bridge between the scientific and administrative worlds of translational research, helping to identify — and find ways to procure — the many resources that will be required to bring the program to the next level. One of the critical factors for success, he said, will be to find ways to provide the financial support that will allow physician-researchers to increase the number of hours they can devote exclusively to their research. He also aims to ensure that adequate staff members are hired to handle the myriad of logistical, administrative and regulatory procedures that are an integral part of conducting clinical trials.

Pivotal point for program

Appelbaum said that bringing Cheever on board at this point in time represents a critical transition in the evolution of the solid-tumor program.

"We have made considerable progress in developing the solid-tumor program and have a number of achievements we can be proud of," he said. "Still, we have a lot more to do. We want to be making a major impact in treating solid-tumor cancers — and one of the best ways we can do that is to have someone on board who can devote 100 percent of their time to continuing to build the infrastructure and mentoring junior faculty. Mac is an outstanding fit for this role."

Cheever describes this point in the evolution of the Center/UW solid-tumor program as both exceedingly exciting and challenging.

"We have enormous potential — but we will need additional resources and staff to realize this potential," he said. "The leaders of both institutions recognize the great value of this investment, and they are committed to seeing it through. Our goal should be nothing less than creating a world-class program."

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