September 18, 2018 | by Letisia Marquez
Just a month shy of their wedding, City of Hope scientist Saul Priceman, Ph.D., and his fiancé, Donna, received some sobering news about her father. Tom Silver was diagnosed with late-stage pancreatic cancer and given less than a year to live.
“It was such devastating news at a time that should have been filled with nothing but happiness,” Priceman said. “But our wedding also provided a great source of joy for Tom and both of our families — something wonderful to look forward to.”
The couple also made a resolution — they would get pregnant as quickly as possible so Silver could see his first grandchild.
“Sadly, that didn’t happen because Tom died just eight months after his diagnosis and our son, Aaron Tom, was born two months later. But he knew Donna was pregnant, felt him in her belly and was a part of it, the wonderful process,” Priceman said. “Aaron is an absolute joy now even though he was born during some very tough times.”
Those difficult months helped Priceman realize why urgency is so important in the work he does every day at City of Hope.
Priceman is an assistant research professor with City of Hope’s T Cell Immunotherapy Laboratory, which has already produced successful chimeric antigen receptor (CAR) T cell therapies for such blood cancers as acute myeloid leukemia and lymphoma, as well as brain tumors. Now, researchers like Priceman are turning their focus on developing more CAR T clinical trials for patients battling solid tumor cancers like breast and prostate cancer.
“Most of us working at City of Hope know someone who has died of cancer, and those memories motivate us all to keep working toward finding more cures for these devastating diseases,” Priceman added.
Priceman, 39, was born in London, England. His father Bernard, an accountant, was born there and his mother Ruth, a flight attendant, took a trip to London after the airline she worked for suffered massive layoffs. Ruth had a friend in England who invited her to another friend’s birthday party. That friend was Priceman’s father.
“They met and fell madly in love,” Priceman said. “They were engaged six weeks later and got married three months later.”
The family moved to Los Angeles after Bernard was offered a head accountant position in Southern California.
After living in Los Angeles for only a few months, Priceman recalled he came home from school one day and asked his mother for “water” instead of “wohta" (the latter being the British pronunciation).
“We were officially Americans,” he said.
Eventually, Priceman’s parents, and later his older brother Mark, became real estate agents in the San Fernando Valley, and the business is still in existence today, known as “The Priceman Team.”
Priceman started to play the piano when he was 8 years old, and he enjoyed music so much that he eventually started producing it. Priceman and a few friends produced hip-hop, R&B and other music, starting in college. It’s a hobby that continues to this day.
They were so successful at it that MTV even picked up some of the music. The songs played as background on such television shows as “Pimp My Ride” and “MTV Cribs.” Priceman and his friends worked with several local artists as well.
“We still get royalties,” he said. “It doesn’t pay the bills, but it’s been a great creative outlet.
Priceman attended University of California Santa Barbara for his undergraduate education, where his passion for research took root. He majored in genetic studies and also volunteered in a lab that did research on fruit fly genetics.
“Because their lifespan was so short, you could understand concepts very quickly in terms of their genetics, and the impact of specific genetic mutations in such a short life span, and try to relate it to human genetics. At that point, I thought I wanted to get a medical degree because I thought that’s what you to do in the medical field. I didn’t know about translational research,” Priceman said.
Once he graduated, Priceman began working in a laboratory at Amgen, a major biopharmaceutical company in Thousand Oaks, California. Priceman was hired to work in a department that focused on understanding a therapy’s “pharmacodynamics,” or how a drug functions in a person’s body.
“I worked with a cancer drug, and it was mind blowing,” he said. “We worked with early phase clinical trials, trying to understand how they worked and how we could improve them in the long run. It was super interesting. I realized during that experience that I had to get a Ph.D., so I left after three years at Amgen and went to UCLA. I wanted to create the therapies that would ultimately cure patients. That was what excited me.”
At the university, Priceman became intrigued by a research concept that few other researchers at the time were following – how a person’s immune system can be used to fight cancer.
“It was a niche and not much focused research was being pursued in that area at UCLA at that time,” Priceman said. “Immunotherapy for cancer is in the news a lot now but back then, it wasn’t. So it’s been exciting to see how much the field has grown.”
He decided to pursue a Ph.D. in tumor immunology and complete his postdoctoral fellowship at an institution where immunotherapy research was a priority. That place was City of Hope.
Priceman came to City of Hope to work in a lab headed by Hua Yu, Ph.D., the Billy and Audrey L. Wilder Professor in Tumor Immunotherapy. The lab focused on STAT3, a protein that drives cancer growth and critically regulates the immune system in cancer patients. In addition to cancer, Priceman also did preclinical research on how STAT3 could drive type 2 diabetes.
Because of his experience working with T cells in his postdoctoral fellowship, Priceman joined the faculty in City of Hope’s T cell immunotherapy program in late 2013.
CAR T cell therapy involves taking immune cells known as T cells from a patient’s bloodstream, and reprogramming them in a laboratory to recognize and attack cancer cells by adding a CAR, a chimeric antigen receptor that redirects the killing activity of the T cells. The CAR T cells are then reintroduced into a patient’s system to target and destroy tumor cells.
CAR T cells have worked so effectively for blood cancers, explained Priceman, because they encounter tumors almost immediately once infused into a patient. With solid tumors, however, what’s known as an "immunosuppressive microenvironment" is a major barrier to T cells.
“A lot of solid tumors have essentially not only shut down the immune system but they’ve also co-opted it to work in their favor,” Priceman added. “So even if you make a CAR T cell that’s really amazing and you intravenously inject it into a patient, it’s a hard feat for the T cell to get to the solid tumor mass and kill cancer cells once inside the tumor because of the local immunosuppressive microenvironment.”
“So a lot of the work in my group is to build a CAR that will allow them to be more potent and survive for longer periods of time in this harsh microenvironment,” he said.
Developing a clinical trial for patients might take years to develop at another institution, if it’s developed at all. But at City of Hope, which has one of most comprehensive CAR T programs in the nation, Priceman notes that two CAR T trials he helped to develop are at the brink of starting since he joined the CAR T lab five years ago.
One CAR T cell trial due to start in the next month or so will be largely for women with HER2-positive breast cancer that has spread to the brain. The trial will be the first in the nation to focus on patients with HER2-positive brain metastases, and also the first to use intraventricular delivery of CAR T cells to the brain of breast cancer patients with HER2-positive brain metastases.
A CAR T cell trial for patients with metastatic castration-resistant prostate cancer, which is anticipated to open in late 2018 or early 2019, uses a specific CAR design that allows for optimal cytokine production (chemical messengers that help enhance the anti-tumor activity of a CAR T cell) and destruction of prostate stem cell antigen-positive prostate cancers by the CAR T cells.
The T cell lab is also working on developing CAR designs for ovarian and pancreatic cancers, which both have low survival rates and for which few CARs have been developed.
It’s a challenge that, of course, holds a deep meaning for the Pricemans.
“Cancer affects the patient and the entire family” Saul Priceman said. “Our hope is that one day we will find tools to eradicate all cancers. City of Hope’s mission is to attack them all, and I truly believe immunotherapy, and CAR T cell therapy in particular, will be the key in doing just that.”
Saul Priceman’s CAR T research is funded by the Prostate Cancer Foundation, Department of Defense, STOP CANCER, California Institute for Regenerative Medicine and Susan E. Riley Foundation, as well as by Barbara Natterson Horowitz, M.D., and Zach Horowitz, Gary Marsh and Jody Horowitz Marsh.