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Mark Yarmarkovich

Children’s Hospital of Philadelphia

Mark Yarmarkovich saw a revolution unfolding in cancer care, and he wanted in. It was around 2012 when the scientist saw early data on CAR-T, a newfangled therapy in which a patient’s own immune cells are rewired to home in on malignant growths. CAR-T was getting dazzling results in a few rare, aggressive cancers, but translating those benefits to other forms of the disease was proving immensely difficult. 

Yarmarkovich, then working on novel antibodies at Genentech, thought he could help, so he turned to the CAR-T pioneers at the University of Pennsylvania and its affiliated Children’s Hospital of Philadelphia. 

Nearly a decade later, Yarmarkovich and his colleagues have made huge strides in solving the puzzle of why some cancers are susceptible to attack while others can shrug off the best modern medicine has to offer. 

Yarmarkovich set out to address a recurring problem in cancer immunotherapy: There aren’t enough targetable antigens, proteins on the surface of cancer cells that can serve as bull’s-eyes for the immune system. Using a lot of traditional biology and some novel computational tools, Yarmarkovich’s team has discovered promising new immunotherapy targets, including one for the vexing cancer neuroblastoma, that promise to expand the utility of treatments like CAR-T.

“Right now this process is very costly and time-consuming, and in its current form would take years from target discovery to having a product,” Yarmarkovich said. “The ultimate vision would be to be able to deploy this in a personalized manner, to be able to take a tumor biopsy, figure out what tumor-specific antigens that patient has, and, within the course of their treatment, have a therapy ready for them.”

That goal — making a lifesaving treatment available to as many people as possible — is part of what led Yarmarkovich to the bench in the first place. Born in Moscow, his family came to the U.S. when he was 3, and he spent much of his education aspiring to become a doctor. But breakthroughs in oncology research soon captured his imagination, and “the ability to tune the immune system and apply that to cancer was something where I thought I could have more impact than working in a clinic,” he said.

— Damian Garde