of mice & medicine: dr. renier brentjens

When I asked Dr. Renier Brentjens why he pursued medicine, he told me about a “probably overly romanticized” view he had as a child of his father, who was also a doctor. He remembers the phone ringing late one night, a call for his dad, from work–he had to take it.

“It was probably minor, something to do with mice in the lab,” he says, in hindsight, “but I had formulated it into something heroic, what a doctor does. So I never wanted to be a policeman or a fireman. I was always going to be a physician.”

And that’s what Renier became. Today, he’s Deputy Director and Chair of the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. 

Born in Amsterdam to two Dutch doctors, Renier spent his early childhood in the Netherlands–but he’s always seen Buffalo, New York, as his hometown. When his father was offered tenure at the University at Buffalo, the Brentjens family relocated to Western New York, living in Williamsville for a short period before settling down in North Buffalo. Renier attended the Waterfront school and then Canisius High School.

He received his undergraduate degree at Davidson College in North Carolina–taking all the necessary prerequisites for a future medical student while majoring in history–before returning home for his MD-PhD at the University at Buffalo. After completing his residency at Yale University in 1998, he moved to New York City for a fellowship at Memorial Sloan Kettering Cancer Center.

It was there at Sloan Kettering that Renier’s career and life would change completely–with a phone call having something to do with mice in the lab.

When Renier joined the lab of Dr. Michel Sadelain in his second year of fellowship, the lab was still in its infancy, under the radar, not yet the sort of lab that fellows fought to join hoping it might get them closer to a Nobel Prize.

Renier chose Sadelain’s lab for the simple reason that the research was interesting to him.

“The thing about science,” he explains, “is that you have to be enthusiastic about it, and you have to enjoy it. And if you’re not excited, if you don’t have faith in what you’re doing, it’s awfully hard to get up on the weekends to come into the lab.”

The idea that excited Renier then, and still excites him today, was the hypothesis that if a cancer patient’s immune cells–“T cells,” the body’s built-in disease fighters–were genetically altered in just the right way, they could learn to recognize, attack, and kill cancer cells. 

The technology to do this kind of genetic engineering was new in the late 90s and early 2000s, but it held the alluring promise of cancer treatment without the same devastating side effects of chemo and radiation therapies.

Renier dove into the work, his enthusiasm propelling him out of bed and into the lab at all hours of the night and into weekends.

In 2002, Renier co-authored the first of a series of pivotal papers focused on what he, Sadelain, and their fellow researchers termed “CAR T cells”–an abbreviation for “chimeric antigen receptor T cells.” These were the genetically engineered immune cells at the center of the lab’s big hypothesis.

The success of these early experiments–where Renier and his colleagues would engineer the CAR T cells and combine them with cancer cells in a dish, then watch as the CAR T cells attacked and killed the cancer cells–indicated it was time to start studying the technology in living organisms. Soon after publication of that first paper, they began mouse studies.

When he talks about this phase of the path to scientific breakthrough he was on, Renier lights up–the mouse studies are one of the milestone moments in his career, and one study in particular changed everything.

The story goes like this: Renier and his colleagues have introduced leukemia cells into 20 lab mice and then split the mice into two groups, one untreated control group, one CAR T cell-treated group. Renier leaves the mice in New York and heads to Ireland on a long-awaited vacation with his wife, Tricia. Tricia is a busy physician herself. She’s also pregnant with their second child, and they’ve locked in her parents to babysit their eldest while they enjoy a break. Renier and Tricia have agreed to take a true vacation–no calls into work. Nine days later, Renier and Tricia touch down at JFK and Renier is on the phone with his colleague at the lab; she’s telling him one group of mice has died, but he can’t get her to elaborate (which group?), so he drops his luggage at home, hugs his son Jan, and dashes to Sloan Kettering. Finally, he gets the answer he’s been chasing–all 10 untreated mice have died. And all 10 of the mice treated with CAR T cells are alive and well.

“Scientists build a career hoping to have just one of these moments,” Renier says of every researcher’s dream: to see their hypothesis proven. “And if you’re a fortunate scientist, you get results like this, so unequivocal…” he trails off before adding, “I didn’t see it this way at the time, but everything in my future hinged on that one damn experiment.”

The results of the mouse study were published in a 2003 paper in the journal Nature Medicine, the experiment’s success opening the door to extraordinary possibilities for patients, doctors, and researchers alike. Renier and his team began clinical trials in human patients not long after.

Years into these clinical trials, Renier would have another once-in-a-career success; this time, it was bigger than mice, and it began with a patient facing a treatment-resistant form of acute lymphoblastic leukemia (ALL), a disease with a very low survival rate for adult patients.

Prior to initiating the treatment, more than half the cells in the patient’s bone marrow sample were leukemia cells, and Renier admits feeling a pang of hopelessness when he saw what was under the microscope. He and his colleagues forged ahead, though, building CAR T cells from the patient’s own immune cells, infusing them back into the patient’s system, and then awaiting the results.

A few days after the infusion, Renier received word that the patient was in the intensive care unit with a high fever. Fever, of course, is indicative of an immune response–and perhaps, Renier thought with some reservation, this was an immune response to cancer.

Another week passed and Renier took a sternal aspirate–a bone marrow sample from the patient’s sternum–back to his lab, where he and his colleagues looked at the results in disbelief.

They were looking at a sample containing no leukemia cells at all, taken from a patient whose pre-treatment sample showed almost entirely leukemia cells.

In 2013, 10 years after the paper outlining the mouse study results was published, Renier and his team published the results of their clinical trial, in which five adults with refractory ALL saw successful results from CAR T cell therapy.

The paper went out in the journal Science Translational Medicine and almost no time at all passed before the story hit mainstream news outlets. Renier found himself on the front page of the New York Times, and at the fore of a new frontier in cancer medicine.

“When I’m asked about the moments I remember,” he says, “it’s always going to be coming back from Ireland, those 10 mice, and the sternal aspirate. Those were the really watershed moments.”

Ever the scientist, ever considering what else is possible, Renier can only pause to reflect on these moments for so long before he jumps topics and starts in on what’s next, what still needs to happen in cancer medicine before we can ever really celebrate.

Since his earliest successes with CAR T cells, Renier has  pushed the idea that the technology that makes them possible can always improve. He defaults to an analogy about cars, where the CAR T cells of the early 21st century are Model T Fords; we need Mustangs now.

“There’s still a lot we have to figure out before we can do this for breast cancer, for colon cancer,” he says. “We have something that, on paper, should work. But there are a bunch of obstacles, and we need to overcome them. What it depends on is that we stay rational as we come up with clever new ways of making CAR T cells better.”

The cells Renier and his colleagues pioneered in the early 2000s are successful in getting patients with “liquid” cancers like leukemia into remission–people across the United States and the world have beaten their cancer diagnoses thanks to the treatments. Now Renier wants to see those same results in patients with other cancers. 

This is the work he set out to do with his colleagues at Roswell Park Comprehensive Cancer Center when he took the job in 2021.

“Roswell is a major, premier cancer center,” he says. With the Center’s collaborative approach to research, treatment development, and patient care, he believes it’s the ideal space for him to bring his vision for better, more effective cancer immunotherapies to life.

And it’s a bonus for Renier that he gets to do it all in Buffalo, in his hometown.