James P. Allison, PhD
Immunotherapy pioneer James P. Allison, PhD, has been named the 2015 recipient of the Lasker-DeBakey Clinical Medical Research Award by the Albert and Mary Lasker Foundation. The award honors investigators whose contributions have improved the clinical treatment of patients.
“I’m honored and grateful to receive the Lasker award,” said Allison, chair of Immunology at the University of Texas MD Anderson Cancer Center, in a statement. “As a basic scientist, I was pleasantly surprised, really, kind of stunned, to receive the clinical award. This award is also important recognition of the early success of cancer immunotherapy and its great potential to extend survival of cancer patients for decades and ultimately to cure some types of cancer.”
Earlier this year, Allison also received the Science of Oncology Award by ASCO and the Pezcoller Foundation–AACR International Award for Cancer Research. He also received the 2014 Giants of Cancer Care® award for Scientific Advances in 2014.
Allison is best known for his work in T-cell response mechanisms and his discovery that blocking the signaling of the immune-checkpoint protein CTLA-4 improved antitumor immune responses. His research led to the approval of ipilimumab (Yervoy), which became the first FDA approved checkpoint inhibitor when it was authorized for the treatment of advanced melanoma in 2011.
In the trial that led to the approval of ipilimumab for patients with unresectable or metastatic melanoma following at least one prior systemic treatment, overall survival (OS) was longer with ipilimumab alone compared with the experimental tumor vaccine gp100 (HR, 0.66; P = .0026). Patients treated with ipilimumab alone had a median OS of 10 months, while those treated with gp100 had a median OS of 6 months. The trial also demonstrated a statistically significant improvement in OS for patients treated with the combination of ipilimumab plus gp100 compared with patients who received gp100 alone (HR, 0.68; P = .0004).
Since its approval, ipilimumab has been investigated in other tumor types, including non–small cell lung cancer (NSCLC) and prostate cancer, as well as in multiple settings within melanoma. Other checkpoint inhibitors, including nivolumab (Opdivo) and pembrolizumab (Keytruda), have been approved for melanoma and lung cancer and are being widely tested in other cancers. Combination clinical trials also are underway, blending multiple types of checkpoint inhibitors and testing them along with radiation, molecularly targeted drugs, and other therapies.
The phase II CheckMate-069 trial showed that nivolumab plus ipilimumab delayed disease progression by 60% compared with ipilimumab alone in patients with advanced melanoma. The checkpoint inhibitor combination had an overall response rate (ORR) of 61% in a subgroup of BRAF V600 wild-type (WT) patients.
Checkpoint inhibition has opened the door to significant advancements in the field of cancer, said Joseph Goldstein, MD, chair of the Lasker Medical Research Awards Jury, Nobel Laureate and chair of Molecular Genetics at the University of Texas Southwestern Medical Center.
“Jim Allison found a way to remove the brakes that stop T cells from fighting tumor cells—a discovery that opens brand new and very effective ways to treat cancer,” said Goldstein in a statement.
Allison has focused much of his career on understanding the immune system and the specific role T cells play in it. In 1982, while he was working at MD Anderson Cancer Center (then named University of Texas System Cancer Center), he became the first scientist to determine how T cells recognize alien proteins within the body.
Later, during his time at the University of California Berkeley, Allison discovered that a second protein on T cells, called CD28, must be engaged for full activation of T cells. He hypothesized that a brake on T cells (CTLA-4) might be blocked to free T cells to attack cancer. Decades of research had indicated that the immune system could try to find and kill tumors, but was somehow thwarted.
Allison and colleagues developed an antibody to plug up CTLA-4. When this was proven effective in mouse models against several cancer types, they sought to have the approach tested in the clinic. They eventually collaborated with Medarex, a company that was later purchased by Bristol-Myers Squibb, and developed ipilimumab in clinical trials.
Allison returned to MD Anderson Cancer Center in 2012 to lead its immunology department and establish the cancer immunotherapy platform, an initiative that aims to bring together scientists and clinicians to better understand and advance cancer immunotherapy.
Allison is MD Anderson’s second faculty member to win a Lasker award. Emil J Freireich, MD, was honored in 1972 for outstanding achievements in chemotherapy combination treatment and supportive care for patients with leukemia. Like Allison, Freireich is also a Giants of Cancer Care award recipient, recognized in 2015 in the category of Lymphoid Neoplasms.
The Lasker Awards program, founded in 1945, has recognized the contributions of scientists, physicians, and public servants who have made major advances in the understanding, diagnosis, treatment, cure, and prevention of human disease.