The Breakthrough by Charles Graeber

Author:Charles Graeber
Language: eng
Format: epub
Publisher: Grand Central Publishing
Published: 2018-11-05T16:00:00+00:00

This was a particularly thrilling time for Chen and Mellman. They were cancer immunologists who actually got to make a cancer immunotherapy drug they believed would work, and they knew how fortunate they were. They had a green light and funding, teams of top researchers, and a potential PD-L1-blocking antibody already on the shelf at Genentech. Their task was to turn that into a real drug for real patients. It wasn’t easy, but for once, it seemed possible.

They started with mouse models. The PD-L1-blocking antibody worked there; it seemed to reopen the road of a stalled immune response to the tumor by blocking the tumor side of the PD-1 / PD-L1 handshake. Once again, cancer was cured in mice. The next step was to make human antibodies against PD-L1 and see how they did blocking the tumor’s handshake in people. Chen would be in charge of the trials.

Six weeks later, in February of 2012, his team got the first scans from their phase 1 clinical trial. The first responder was patient 101006 JDS: Jeff Schwartz. That was a thrilling moment, but it was just one patient, with kidney cancer. Chen’s boss on the clinical trials side was Dr. Stuart Lutzker, who’d told Chen he’d believe this immunology approach when Chen could show him proof it worked in lung cancer, the leading cause of death globally and Lutzker’s specialty. But Chen had scans from a lung cancer patient too. He wasn’t a full responder yet, but something was changing after he went on the drug. Chen saw that the patient’s tumors, which previously had a rounded mass, now had a spiny appearance, as if the tumor was pulling back and retracting along these spikes rather than continuing to grow into the surrounding lung. “Each tumor type has a sort of personality,” he explains, “a signature unique to it, and when it begins retreating and dying, that also has a unique appearance on the scan.” Chen remembered bringing the scans up to Lutzker’s office. “He just looked at it and said, ‘This isn’t what a growing tumor normally does. This is real.’”

“It just transformed his opinion one hundred eighty degrees. And remember, he’s a cancer biologist,” Chen says. His boss had agreed to the company direction, but until then, Chen felt he wasn’t fully convinced; he knew the history of immunotherapy. There was a chance that this, too, would end up being one of those stories that didn’t translate reliably into a drug for a human cancer population, an expensive and humiliating dry run. “But right then he went from being very much against it, to OK’ing the whole new direction.”

Until it was made public, Chen couldn’t have access to all the data from the anti-PD-1 drug trials, which were further along but run by another drug company. But for anti-PD-L1, he was the center of the data spiderweb, in touch with all the clinical investigators. “We immediately started seeing responses,” he says. “And these responses were unlike anything we were used to.

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