There was a time when our only weapons against cancer were blunt ones — chemotherapy and radiation that kill diseased cells but do considerable damage to healthy tissue along the way.
Fortunately, a dramatic shift has been occurring. Bold ideas about more-targeted, less-toxic therapies have begun to enter the mainstream. And Dr. David Maloney has played a pivotal role in getting them there.
Maloney is known for dedicating himself with a singular focus to learning the skills he needs to master everything from woodworking to fishing to photography. It’s the same focus he has applied to his dual vocation as a world-renowned researcher and physician over the past decades.
Known for his gentle, compassionate demeanor with his blood cancer patients, Maloney draws on his experiences in the clinic as he conducts his research on new treatments. Now the Leonard and Norma Klorfine Endowed Chair for Clinical Research at Fred Hutch, Maloney's work focuses on developing and improving cancer treatments known as immunotherapies, which harness the power of the body's immune system to fight disease.
As a doctoral and medical student in the early 1980s, Maloney was part of a Stanford University team that made a landmark discovery. They found that it is possible to create and deliver a type of immune protein called a monoclonal antibody that targets a patient's cancer cells — in this case, non-Hodgkin lymphoma — but largely spare normal cells. "At that time there was much skepticism that antibodies would amount to anything," Maloney recalled. "It has ended up now being a mainstay of cancer therapy."
Building on this discovery, Maloney led the initial development and testing of a now-widely used drug called rituximab, which works by targeting a protein unique to many lymphomas. The major benefits of this approach, Maloney said, are that the antibodies are relatively simple to produce in great enough quantities to serve many patients and that they generally produce few toxic side effects. In 1997, the drug became the first antibody-based cancer treatment on the market. It has since been used to treat more than 1 million patients with non-Hodgkin and follicular lymphomas and has helped to propel the development of other antibody-based therapies for a wide range of cancers.
Maloney called the emergence of rituximab “paradigm-changing,” the biggest breakthrough in lymphoma therapy in 25 years.
Since his arrival at Fred Hutch in 1994, Maloney has continued to make breakthroughs for patients. Working with colleagues Drs. Rainer Storb and Brenda Sandmaier, he has helped to develop new and improved procedures for blood stem cell transplants, which can save the lives of patients with a variety of serious blood disorders. Those improvements include the “mini-transplant”, whose reduced intensity has brought the lifesaving power of transplants to older and sicker patients who once were not medically eligible for the procedure. In a mini-transplant, a patient’s own immune system is not entirely destroyed before donor cells are transplanted, which “taught us the immune system is able to eradicate a lot of tumor,” Maloney said.
As the first medical director for cellular immunotherapy at Fred Hutch and the Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance (Fred Hutch’s patient-care arm), Maloney is still focused on making the next big breakthrough: developing personalized therapies in which a patient’s own immune cells are genetically reprogrammed to eliminate their cancer.
Now in early-phase clinical trials, these so-called CAR T cells are astounding Maloney and his colleagues with their activity against advanced blood cancers that have proved intractable to other cancer therapies ― for example, in one trial in acute lymphoblastic leukemia, the complete remission rate soared upwards of 90 percent.
“In early-phase trials, you’re continually learning. You don’t expect results like these from early-phase trials. That’s why these response rates are so extraordinary,” Maloney said.
These T cells target cancer cells because they have been engineered with a synthetic molecule called a CAR, or chimeric antigen receptor. The backbone of a CAR is an antibody, the type of cancer-targeting protein Maloney has worked on for decades.
Looking back on his career so far, Maloney is proud of how he has played a role in transforming cancer care. But he says that what he and his teammates have achieved so far with CAR T cells, and the potential this experimental therapy has for helping patients in the future, is the most exciting thing yet ― “better than all the rest of them put together.”
― Updated Nov. 14, 2016