An NCI-designated Comprehensive Cancer Center
By Wayne Lewis | April 2, 2018
CAR T Trio Researchers | City of Hope From left: Catherine Matsumoto, Araceli Naranjo and Jamie Wagner

It takes a city to translate breakthroughs into treatments.

In the case of CAR T cell therapy — which re-educates immune cells to attack blood cancers and other diseases — dozens of researchers and physicians throughout City of Hope contribute to its momentum.

Often unrecognized, however, are the countless folks who work in the spaces between the lab and the clinic — a group of people responsible for doing everything from manufacturing CAR T cells to gaining federal approval for new trials.

Meet Araceli Naranjo, Jamie Wagner and Catherine Matsumoto, each of whom works behind the scenes within City of Hope’s CAR T program. Both Naranjo and Wagner work under the direction of Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, and Christine Brown, Ph.D., the Heritage Provider Network Professor in Immunotherapy within the T Cell Therapeutics Research Laboratory. Matsumoto is City of Hope’s director of regulatory affairs.

We sat down with the trio as they revealed six things they’ve learned along the way.

Lesson #1: Things don’t always move in a straight line

It sounds like a straightforward process.

Researchers send specifications for a CAR T cell to Naranjo, the staff scientist who oversees manufacturing at City of Hope’s Cellular Therapeutics Production Center.

She works out the logistics of re-engineering the cell and shares them with Wagner, regulatory operations manager, who writes up an investigational new drug (IND) application for the Food and Drug Administration (FDA). In addition to information about the manufacturing process, the application includes preclinical data and the clinical protocol.

The application is reviewed, packaged and sent to the FDA by Matsumoto, an institutional liaison whose team handles all City of Hope IND applications.

But things aren’t quite that simple. “We constantly go in a circle,” Wagner said.

In a dynamic collaboration, the three work together closely to describe the production process that will pass muster with regulators and to address any feedback Matsumoto gets from the FDA. Time is of the essence, since City of Hope must receive FDA go-ahead before patients can receive therapy through a trial.

Lesson #2: The cliché is true — it’s all about teamwork

The collaboration between Naranjo, Wagner and Matsumoto gains from their shared history. CAR T cells were the first products made in City of Hope’s Center for Biomedicine & Genetics (CBG), and all three were there, more or less elbow-to-elbow, from day one.

Then, Naranjo and Wagner worked together in manufacturing, while Matsumoto handled quality assurance. Though roles have shifted over the years, their work today benefits from their longtime association.

“The three of us pretty much finish each other’s sentences,” Wagner said.

Wagner and Matsumoto also grasp the vagaries of cell production thanks to those early days. Matsumoto noted, “Because I’ve had exposure to manufacturing when I worked in the CBG, it’s easy for me to understand the process.”

Lesson #3: A little intellectual curiosity goes a long way

In addition to cultivating regulatory staff with valuable hands-on experience, City of Hope is producing CAR T cells under the supervision of Naranjo, who’s already been making them for two decades.

Naranjo credits these advantages to the leaders who encourage staff to learn and grow. Beyond enabling people to move into new roles, she has seen how stimulating curiosity promotes efficiency.

“We can try things out,” she said. “We can figure out how to make our processes better and stronger.”

Lesson #4: It all comes down to the patients

From home base in the Arnold and Mabel Beckman Center for Cancer Immunotherapeutics & Tumor Immunology, Naranjo and Wagner can look across the way to CIty of Hope Helford Clinical Research Hospital, where patients in trials receive infusions of therapeutic CAR T cells. The view is a daily reminder for them about the stakes of their work.

“Speaking for all my team, the fulfilling part of this job is helping patients as quickly as we can,” Naranjo said.

Matsumoto echoed the sentiment.

“I’ve really enjoyed seeing that, after many years of working on CAR T cell therapies, we’re starting to see benefit to patients,” she said.

Lesson #5: Everybody is rooting for a cure

Helping patients through City of Hope’s CAR T cell research excites people beyond campus as well. Makers of scientific instruments consult with Naranjo, seeking to modify or create equipment to assist manufacturing.

“Companies love hearing about how they can make the process better,” Wagner said.

Meanwhile, FDA regulators also help move trials forward quickly and safely.

“Working closely with the FDA, I’ve seen that they really want us to succeed in getting treatments into the clinic,” Matsumoto said. “They encourage us to talk to them early to make sure we’re following the appropriate strategy. Especially with the CAR T cell, they’ve provided some very useful feedback.”

Lesson #6: A Career in science doesn’t have to take you to the usual places

All three colleagues earned undergraduate degrees in science. At City of Hope, that training has taken them places they did not expect.

“When you’re younger, you think you can only go into medicine, teaching or research,” Matsumoto said. “But in reality, there are so many other options.”

Naranjo visits low-income schools to tell students about her work. Her message is simple: A career in science is attainable.

Naranjo said: “I tell them, ‘I grew up in East L.A. and I’m working in a lab at City of Hope.’ The little girls say, ‘No way!’ And I just say, ‘You can do it, too.’”



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