The 2019 Lasker-DeBakey Clinical Medical Research Award has been granted to scientists H. Michael Shepard, PhD, Dennis J. Slamon, MD, PhD, and Axel Ullrich, PhD, for their development of the breast cancer therapy Herceptin (trastuzumab).
The Lasker Awards are widely regarded as America’s most prestigious biomedical research awards and have been honoring key contributions to the understanding, diagnosis, treatment, cure, or prevention of human disease. A total of $250,000 are given in each of its categories. The awards will be presented on Friday in New York City.
Having been approved in the U.S. in 1998 for patients with an aggressive form of breast cancer (HER2-positive), Herceptin was the first monoclonal antibody therapy binding a protein coded by an oncogene — a gene that, when mutated, can cause cancer — and one of the earliest designed to block cancer growth. More than 2.3 million patients have been treated with Herceptin to date.
Developing treatments to target oncogenes had been proposed as a likely effective cancer treatment strategy in the mid-1970s. Shepard and Ullrich, then working at Genentech, and Slamon, at the University of California, Los Angeles, provided the first evidence that monoclonal antibodies could treat solid tumors successfully.
Ullrich and Shepard had shown in preclinical studies that antibodies could reduce the proliferation and survival of HER2-positive breast cancer cell lines. But it was only after they developed a “humanized” version (one developed in mice and then adapted not to trigger an immune response) that researchers were able to proceed to clinical trials.
In a recent article in The New England Journal of Medicine, “HER2 and Breast Cancer — A Phenomenal Success Story,” Daniel F. Hayes, MD, said awarding Shepard, Slamon and Ullrich “should come as no surprise, but rather with a great deal of satisfaction and happiness,” as their work “launched a new era in clinical research and the practice of oncology.”
Hayes, the clinical director of the Breast Oncology Program at the University of Michigan Rogel Cancer Center, detailed the development of Herceptin, including his own participation in the Phase 2 trial, led by Slamon, testing add-on treatment with chemotherapy.
Virginia, a breast cancer patient taking part in this study, stood out. After failing treatment will all other possible medications, she had “a nearly miraculous response, with complete resolution of her pulmonary and hepatic metastases and dramatic improvement in her quality of life,” Hayes wrote.
Seven other trials later showed that using Herceptin with chemotherapy extends survival and reduces mortality of patients with HER2-positive breast cancer. Subsequent anti-HER2 therapies brought even greater benefits.
Investigators now are exploring combinations of HER2 inhibitors with other approaches such as immune checkpoint inhibitors, as well as alternatives to make treatment more affordable.
“The oncologic medical community and, more importantly, our patients owe Drs. Ullrich, Shepard, and Slamon and the numerous other laboratory, translational, and clinical investigators who have played a role in this remarkable story a great debt of appreciation,” Hayes said. “The terms “game changer” and “blockbuster” are worn, but in this case the ingenuity, vision, and persistence of these collaborators justify these superlatives.”
The 2019 Albert Lasker Basic Medical Research Award will be given to Max D. Cooper, MD, from Emory University, and Jacques Miller from the Walter and Eliza Hall Institute of Medical Research, in Australia. Cooper and Miller had a key role in setting the organizing principle of the adaptive immune response and laying the groundwork for current immunology research.
While immune B-cells produce antibodies specific to invader organisms, T-cells mature in the thymus and act by helping B-cells detect pathogens, as well as by identifying and killing infected or abnormal cells.
Miller first showed that the thymus is key for immune function, with Cooper then finding B- and T-cells as two distinct cell lineages in the adaptive immune system. He also characterized B-cell development through work in chickens, while contributions from Miller and colleagues showed the importance of the interaction between these two cell types and how B-cells’ production shifts from the liver to the bone marrow after birth.
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