The Albert and Mary Lasker Foundation today named five researchers and an organization that promotes vaccination of children in underdeveloped countries as winners of its annual awards for work that has advanced the potential translation of basic science into addressing unmet medical needs, as well as the practice of public health.
The awards will be presented on September 20 in New York City.
Max D. Cooper, MD, of Emory University School of Medicine, and Jacques Miller, PhD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, were named winners of the 2019 Albert Lasker Basic Medical Research Award for their seminal work in uncovering the organizing principle of the adaptive immune response by identifying and defining the function of B and T cells.
The discoveries have defined the field of adaptive immunity and have served as the building blocks for current immunology research and clinical advances, according to the Foundation.
B cells develop in the bone marrow and respond to pathogens by disabling them or tagging them for destruction through the production of antibodies. T cells, which mature in the thymus gland, can also detect and kill infected or abnormal cells, helping alert B cells to the presence of pathogens.
“At the molecular level, those cells cross talk with each other,” Miller said during a teleconference with reporters in which he and all but one of this year’s other winners discussed their work. “B cells need the help of T cells to produce very strong antibodies. Without T cells, the B cells cannot in many cases produce the correct antibody. They need help from the T cells.”
Miller showed the importance of the thymus in immune function, while Cooper demonstrated the presence of B cells and T cells as two distinct cell lineages in the adaptive immune system. Working with chickens, Cooper showed that an avian organ called the bursa of Fabricius is where B cells mature and characterized the different stages of B cell development. Miller later established that interactions between B and T cells are essential to their normal maturation and function, while Cooper and colleagues showed in mammals how B cells are generated in the liver of the fetus and the bone marrow after birth.
“We thought that it might be clear what the thymus and bursa were doing if we could eliminate cells that had developed before the chicks hatched, and then removed the bursa or the thymus at that time, and see what immune system capabilities would develop afterward,” Cooper recalled. “Removal of the bursa wiped out humoral immunity, wiped out plasma cells and antibody production entirely, although the thymus and its dependent system was still intact. So basically, that was a starting point that led us to realize that there were two lineages—one thymus dependent T cells, the other bursa-dependent B cells.”
“We thought that the model that we could create using information from others had implications for understanding better the malignancies of the immune system in humans, defects in antibody production, and cell mediated immunity in patients with unusual viral infection susceptibility,” Cooper added.
At Emory, Cooper is Georgia research alliance eminent scholar, professor of pathology and laboratory medicine, member of the Emory Vaccine Center and the Center for AIDS Research.
Miller joined the Walter and Eliza Hall Institute in 1966 at the invitation of its director, Sir Gustav Nossal, to lead the institute’s experimental pathology unit. He retired in 1996, but continues to be actively involved in immunology research at the institute.
Pioneering monoclonal antibody
Two former Genentech executives, H. Michael Shepard, PhD, and Axel Ullrich, PhD, now of the Max Planck Institute for Biochemistry, along with Dennis J. Slamon, MD, PhD, of University of California, Los Angeles (UCLA), were awarded the 2019 Lasker-DeBakey Clinical Medical Research Award. The three were honored for their pioneering research in inventing Herceptin® (trastuzumab), the first monoclonal antibody shown to block a cancer-causing protein, and for the drug’s development as a life-saving therapy for women with breast cancer before Genentech’s acquisition by Roche in 2009.
Herceptin is a HER2/neu receptor antagonist indicated for HER2-overexpressing breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Herceptin won initial FDA approval in 1998 based on data showing that the treatment coupled with chemotherapy stalled HER2-positive breast cancer progression and extended survival compared to chemotherapy treatment alone.
Complementary research by Shepard and Ullrich at Genentech, and by Slamon at UCLA, offered the first demonstration of monoclonal antibodies as a viable and effective strategy to treat solid tumors, opening a new path to develop and deploy antibodies to treat cancer, the Foundation stated.
“Our work started after I learned about the terrible toxicity associated with most cancer chemotherapies. Then, our goal became to find an effective cancer therapy that killed tumor cells but not normal tissue,” recalled Shepard, who in February was appointed by Anpac Bio-Medical Science to its Technical Advisory Board.
Shepard and colleagues found that highly expressed tyrosine kinases made tumors resistant to immune system attacks by macrophages and the innate immune system.
“The question was, if we could downregulate the HER2 oncogene on tumor cells, could we make them again sensitive to killing tumor cells and the innate immune system? We were very surprised and happy and excited when we put one of our antibodies on tumor cells that overexpressed HER2, they did become sensitive again to immune cell killing,” Shepard said. “After that, we thought that we had a tiger by the tail, and we never gave up working together with Dennis Slamon to get the drug out to patients.”
Slamon said he and colleagues were “on a search mission” for genetic alterations that may play a role in causing cancer. He partnered with Ullrich after he gave a talk about oncogenes at UCLA, where Slamon is director of clinical/translational research, and director of the Revlon/UCLA Women’s Cancer Research Program at Jonsson Comprehensive Cancer Center.
“We asked him about collaborating on using those [oncogenes] as probes,” Slamon said. “As we were screening those major cancers, we found that with the HER2 probe, we saw an alteration that was occurring in about 20% to 25% of human breast cancer.”
That alteration—not inherited, but acquired by individuals—was overexpression of HER2. “When we looked at the clinical data from the patients whose tumors contained this alteration, we found that it was associated with a much more aggressive subtype of breast cancer” that led to rapid recurrence of the disease and shorter survival rate.
“There was smoke there, but the question was, could there be fire?” Slalom added. “When we added the antibody to the human breast cancer cells that had the alteration, we found that it profoundly inhibited their growth in a culture plate. And when we put it into animals and formed human tumors in mice, we found that the antibody had been administered to the mice would significantly inhibit or completely inhibit the growth of those tumors. That gave us our first idea that perhaps this alteration clearly was playing a role in the disease process.”
Ullrich, who was not on the teleconference, served as director of the Max Planck Institute for Biochemistry from 1988 to 2016, when he took the position of emeritus scientific member.
Broadening access to vaccines worldwide
Gavi, the Vaccine Alliance, was awarded the 2019 Lasker-Bloomberg Public Service Award, which honors individuals or an organization whose outstanding public health practice has been deemed to profoundly enhance lives. Gavi was created in 2000 to unite public- and private-sector partners in fostering equal access to new and underused vaccines for children in the world’s poorest countries.
According to Gavi and UNICEF, support from the organization has contributed to the vaccination of more than 760 million children worldwide, resulting in the saving of more than 13 million lives in 73 countries.
“Today, we’re able to reach 86% of children in the world with a third dose of DPT vaccine. That’s an incredible accomplishment,” said Gavi CEO Seth Berkeley, MD. “It also means that 14% aren’t being reached. How do we extend coverage to that last group? In doing that, you not only bring all the life-saving vaccines we have, but you also prepare the ground for when new vaccines appear.”
“Science, I’m convinced, will bring us malaria vaccines, TB vaccines, and ultimately, hopefully, an HIV vaccine, so building out these systems are absolutely critical,” Berkeley added. “These are problems that are solvable, and obviously they’re critical, ultimately, to allowing people to afford a health system that really works for them.”
For 74 years, the Lasker Awards have honored scientists, clinicians, and public citizens worldwide who have made major advancements in the understanding, diagnosis, treatment, cure, or prevention of human disease. Each award category includes an honorarium of $250,000.
Recipients of the Lasker Medical Research Awards are selected by an international jury chaired by Joseph L. Goldstein, recipient of the 1985 Lasker Award for Basic Medical Research and the Nobel Prize in Physiology or Medicine. Lasker-Bloomberg Public Service Award winners are selected by a jury chaired by Alfred Sommer, winner of the 1997 Lasker Award for Clinical Medical Research. Eighty-eight Lasker laureates have received the Nobel Prize, including 39 in the last three decades.