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On immunotherapy trial, long-term survivors of deadly skin cancer point to a hopeful future

Once unheard-of survival rates seen among patients with advanced Merkel cell carcinoma

Feb. 6, 2019 | By Susan Keown / Fred Hutch News Service

Cartoon diagram showing the receptors mediating the interaction between a tumor-specific T cell and a tumor cell or antigen-presenting cell. Diagram shows the T cell receptor binding to the tumor antigen presented by the MHC. Other interactions are shown between PD-1 on the T cell and PD-L1 on the other cell, and between B7 on the other cell and both CD28 and CTLA-4 on the T cell.

The trial tested a drug called pembrolizumab that interferes in one of the complex interactions between tumor-specific immune cells, or T cells (top) and tumor cells. Specifically, trial participants with advanced Merkel cell carcinoma received a drug designed to interfere in the interaction between cell components called PD-1 and PD-L1, at left, a "braking" system that tamps down the immune response.

Diagram courtesy of Dr. Paul Nghiem. Modified from Drake CG et al. Nature Reviews Clinical Oncology 2014, 11:24-37.

More than two-thirds of people with an advanced form of a rare skin cancer are on track to survive at least two years after starting an immunotherapy drug on a landmark clinical trial, researchers reported Wednesday in the Journal of Clinical Oncology.

That’s a profound shift for this deadly cancer, Merkel cell carcinoma, or MCC. Just a few years ago, patients with advanced MCC would invariably receive chemotherapy, the previous standard of care. As many as three-quarters of them would die within that two-year time frame, previous studies have shown.

The investigators are “thrilled” that so many of the trial participants are doing so well compared to what historical data would predict, said Dr. Martin “Mac” Cheever of Fred Hutchinson Cancer Research Center, one of the leaders of this first-of-its-kind study.

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How a phone call helped shape the field of bone marrow transplant

A lifesaving new leukemia treatment was harming some patients’ digestive organs, and no one really understood why. So, over 40 years, Dr. George McDonald helped fill in the gaps.

Jan. 30, 2019 | By Jake Siegel / Fred Hutch News Service

Dr. George McDonald

Dr. George McDonald

Photo by Robert Hood / Fred Hutch News Service

It was August 1972, and Dr. George McDonald was mystified.

Just two months into his fellowship, the young physician was fielding consultation requests for patients with gastrointestinal and liver problems. But the phone call from Dr. Don Thomas was different. The future Nobel Prize winner, whom he’d never met, had mentioned bone marrow transplantation and a sick patient and something called "graft-vs.-host disease." Could McDonald come do a consult?

Of course, he replied. Then he hung up the phone.

“I had no clue what he was talking about,” McDonald recalled.

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Dr. Arvind Subramaniam receives grant to study how cells cope with stalled protein synthesis

National Science Foundation CAREER Award will enable him to develop computational models of this fundamental biological process

Jan. 30, 2019 | By Sabrina Richards / Fred Hutch News Service

Dr. Arvind "Rasi" Subramaniam

Dr. Arvind "Rasi" Subramaniam

Photo by Robert Hood / Fred Hutch News Service

Fred Hutchinson Cancer Research Center computational and molecular biologist Dr. Arvind “Rasi” Subramaniam has received a five-year, $920,000 CAREER Award from the National Science Foundation to develop computational models of how cells cope with stalled protein synthesis. Cells rely on proteins for all their functions, and Subramaniam's research will shed light on how protein synthesis goes awry in diseases such as cancer.

CAREER Awards support early-career faculty poised to make important scientific advances and serve as academic role models in research and education.

“It gives us an opportunity to explore a direction we would otherwise find very hard to do with traditional funding mechanisms,” said Subramaniam, who has also obtained National Institutes of Health funding to study the same process in human cells. “The NSF is more willing to fund projects that are not directly medically relevant. It’s fantastic. A precise understanding of biology is what we want, but you can’t start with a complex disease system. This gives us a really nice way to test our intuition using rigorous computational models.”

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