The 2019 Lasker Award winners were announced Tuesday, adding five researchers and GAVI, the Vaccine Alliance, to its roster of Laureates.

Michael Shepard and Axel Ullrich, both of whom were at Genentech Inc. at the time of the Lasker-winning research, and Dennis Slamon, of the University of California at Los Angeles, jointly won the Lasker-DeBakey Clinical Medical Research Award "for their invention of Herceptin, the first monoclonal antibody that blocks a cancer-causing protein, and for its development as a life-saving therapy for women with breast cancer."

Herceptin (trastuzumab, Roche Holding AG) was "the first fully humanized monoclonal antibody for the treatment of solid tumors, the first approved tyrosine kinase inhibitor, and the first successful biomarker-driven drug development program in cancer," Shepard wrote in a perspective published in the Sept. 10, 2019, issue of the Journal of the American Medical Association (JAMA).

In a press call, Shepard reminisced that "our work started after I learned about the terrible toxicities associated with most cancer chemotherapies," leading him to search for treatments that could selectively kill tumor cells but not normal cells.

That goal ultimately led Shepard, Ullrich and their colleagues to the receptor tyrosine kinases. "As we studied the interaction between tumor cells and the immune system, we discovered that highly expressed tyrosine kinases made tumors resistant to immune system attacks by macrophages and the innate immune system."

Those findings suggested that down-regulating those kinases might re-sensitize tumor cells to the immune system.

The team zeroed in on HER2/Erbb2, and connected with Slamon, after Ullrich gave a seminar at UCLA that Slamon attended.

Slamon and his group decided to test for the oncogenes Ullrich talked about in his patients, and saw that about 20% to 25% of them showed overexpression of HER2, and that such overexpression was associated with "a much more aggressive type of breast cancer" that responded poorly or not at all to existing treatments.

The Genentech team, meanwhile, showed that reducing the expression of HER2 did re-sensitize tumors to destruction by the immune system.

"After that," Shepard said, "we thought we had a tiger by the tail, and we never gave up."

The Albert and Mary Lasker Foundation also awarded the 2019 Albert Lasker Basic Medical Research Award to Max Cooper and Jacques Miller "for their discovery of the two distinct classes of lymphocytes, B and T cells." The Lasker-Bloomberg Public Service Award went to GAVI, the Vaccine Alliance, "for providing sustained access to childhood vaccines around the globe, saving millions of lives, and for highlighting the power of immunization to prevent disease."

More statues for Genentech's Lasker shelf

The award marks the second time that work done at Roche subsidiary Genentech has been honored with a Lasker award.

In 2010, Napoleone Ferrara won the clinical research award for the development of anti-VEGF therapy for wet age-related macular degeneration (AMD). Ferrara is now at the UCSD School of Medicine, but was a fellow at Genentech when he did the VEGF research that ultimately led to the development of Avastin (bevacizumab) and Lucentis (ranibizumab).

Additionally, Genentech founder Herb Boyer was honored in 1980, and executive vice president Richard Scheller in 2013, with the basic research award. Those awards, however, were for research that was conducted at UCSF and Stanford University, respectively.

In his JAMA editorial, Shepard credited the atmosphere at Genentech for enabling the development of Herceptin. "The research environment at Genentech, including ambition and a 'take no prisoners' dedication to good science, was an essential contributor to the success of this project," he wrote.

Slamon, on the other hand, credited Shepard.

"It was in large part Mike [Shepard's] tenacity within the company that kept the program alive... even though there wasn't, I'll say uniform enthusiasm at the company at the time," Slamon told reporters on a press call.

Several attempts to use antibodies for treating solid tumors had recently failed in clinical trials, and though Genentech was... "phenomenal to work with" overall, the company was also smarting from two cancer clinical trial failures in a row.

As a result, groundbreaking as it was, Herceptin nearly didn't see the light of day.

Today, Herceptin is one of three Genentech drugs that target HER2, along with Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). According to the Lasker Foundation, 50,000 cases of HER2-overexpressing breast cancer are diagnosed annually in the U.S., and more than 2.3 million individuals have been treated with Herceptin since its approval.

No Comments