A member of The Checkpoints, a traveling onco-blues-rock band that performs at blues clubs packed with cancer specialists attending meetings around the country, has just received the 2015 Lasker-DeBakey Clinical Medical Research Award, which honors investigators whose contributions have improved the clinical treatment of patients.
Lasker awards “often presage future recognition by the Nobel committee,” according to the Foundation’s website.
James P. Allison, of the University of Texas MD Anderson Cancer Center, was honored today for the “discovery and development of a monoclonal antibody therapy that unleashes the immune system to combat cancer,” according to the Lasker Foundation.
“Nobody deserved this award more than Jim,” said his cancer research and musical colleague Thomas Gajewski (above, left), professor of medicine at the University of Chicago and the Checkpoint’s guitarist. (Allison, center, sings and plays harmonica.) “He changed the field and drove the idea of immune checkpoint blockade as a treatment for cancer. These drugs were first approved in melanoma, but now are proving effective in many types of cancer.”
“By blocking a protein that normally restrains the body’s natural ability to attack tumor cells,” the Lasker Foundation notes, “Allison devised a fundamentally new strategy for treating malignancies. Because this approach targets immune cells rather than specific tumors, it holds great promise to thwart diverse cancers.”
Allison’s early work at the University of California, Berkeley, stimulated controversy, but in the mid-1990s, two former University of Chicago scientists—Jeffrey Bluestone, now at the University of California, San Francisco, and Craig Thompson now at New York’s Memorial Sloan-Kettering Cancer Center—along with Allison determined that a specific protein on the surface of immune cells called, CTLA-4, actually inhibited rather than activated the immune system. Allison went on to show that this off-signal was important in cancer immune evasion.
Allison’s work led to the notion of checkpoint blockade. By using antibodies to the signals that interfere with an immune response, he thought, maybe he could take the brakes off the immune response. This would liberate T cells to attack cancer cells.
It worked. In the laboratory, animals treated with checkpoint blockers rejected their tumors. These liberated T cells could also remember tumors, even months later. They would respond forcefully against tumor cells injected long after the original experiment. They could also battle established tumors.
The US Food and Drug Administration approved the first checkpoint inhibitor, an antibody called ipilimumab, for late-stage melanoma in 2011. More than 20 percent of 5,000 individuals treated with the antibody were still alive ten years after treatment.
A group from Japan soon found another checkpoint blocker. Antibodies against this second checkpoint, called PD-1, received FDA approval for treatment of metastatic melanoma in 2014, and for metastatic squamous non-small cell lung cancer in 2015. There are now than 500 clinical trials under way to explore whether these agents can defeat many types of malignancies, including ovarian cancer, bladder cancer, head and neck cancer, and gastric cancer.
Allison’s work has “cracked open a brand new therapeutic world that capitalizes on the body’s inherent capacity to quash malignant cells,” the Lasker release states. His discoveries are transforming cancer treatment and the prognosis for individuals with these life-threatening diseases.
“This work has changed how we treat many types of cancer,” Gajewski said, “not just melanoma. Our Cancer Immunotherapy program at the University of Chicago is leading several high-profile clinical trials, including studies in head-and-neck cancer, mesothelioma, bladder cancer, and triple-negative breast cancer. There are now more than 20 trials of immunotherapy approaches underway for a wide variety of tumor types.”
“A lot of people,” he added, “are now alive who would not be if Jim Allison hadn’t driven the idea of checkpoint inhibitors into clinical development. We all, patients and physicians, owe him our gratitude and it is fantastic to see his work recognized by the Lasker award.”
“We also need to acknowledge,” he added, “that this guy can play the harmonica.”