An NCI-designated Comprehensive Cancer Center
By Maxine Nunes | January 4, 2018
Xiuli Wang, CAR T for multiple myeloma | City of Hope This image, from a recent paper by Xiuli Wang, Ph.D., shows shows the interaction (in yellow) between CS1 CAR T cells (green) and tumor cells (blue).
At six in the morning, and even on Saturdays, you’ll often find Xiuli Wang, Ph.D., at her laboratory at City of Hope. Her work is so compelling, she just can’t stay away.

“All my passion,” she said, “is focused on finding a cure for hematological malignancies.”

It’s a quest she’s pursued across three continents, from China to Norway to the U.S. and City of Hope, where her search is finally paying off.
 
Wang, a research professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, is at the forefront of one of the most exciting breakthroughs in cancer treatment: chimeric antigen receptor (CAR) T cell therapy.

CAR T is a process in which the T cells from a patient’s own immune system are extracted, multiplied in the laboratory, engineered to target specific cancers, then infused back into the patient.
 
Xiuli Wang 300x300 Xiuli Wang, Ph.D.
CAR T therapy appears particularly promising with blood cancers. In one recent trial, Wang partnered with Samer K. Khaled, M.D., assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation. The trial, designed for B cell leukemia patients, was an extraordinary success.
 
After 11 years dedicated to CAR T research at City of Hope, Wang couldn’t be more thrilled with the results. “It’s amazing,” she said, “just amazing.”

 

A Physician Turns to Research

Wang’s career began in her native China, where she was a physician specializing in hematology, but each day she faced the heartbreaking reality of what her patients — often children, young adults and new mothers with leukemia — had to endure.

“I saw that they suffered a lot, with bleeding, fever, infections,” she said. “Many of them died. It was a nightmare.”

As a physician, Wang had no way to help them, so she decided to pursue a career in research to find an effective therapy for blood cancers.

From China, she set off for Oslo, where she got a Ph.D. in hematology, then moved on to the U.S. for postdoctoral work at Children’s Hospital Los Angeles. Then she heard about City of Hope and their groundbreaking research in CAR T cell therapy for leukemia and lymphoma. That was the work she’d been searching for.

 

Persistence Pays Off

Wang joined the research team at City of Hope in 2006, and the first problem she tackled led to a crucial breakthrough.

“At that time, no one knew if CAR would work or not, because the CAR T cells did not persist and disappeared in the body rapidly,” she said. “So at the beginning, my research focused on how to make them persist after infusion.”

First, Wang found the source of the problem — the cells they were infusing were a mix of old and young. The old cells died off quickly, but the young cells had long lives.

The next step was figuring out how to isolate the long-lived T cells, and Wang discovered a marker, CD62L, found only on young cells. Now, they could isolate and extract only the T cells that would last in the body.

In 2013, phase 1/phase 2 clinical trials began to test the endurance of CAR T cells after infusion. Three years later, Wang published the results. The cells were so long lasting — and continued to reproduce so effectively in the body — that only a single infusion was needed to maintain them.

The next step was maximizing their efficacy as cancer fighters. Wang and her colleagues then began experimenting with new vectors — modifications of the T cells that might more effectively target blood cancers.
 

 

Advantages of CAR T over Other Cancer Therapies

The excitement CAR T therapy is generating is due to some significant advantages over traditional cancer therapies, such as chemotherapy.

Chemotherapy kills not only cancer cells, but also normal cells,” Wang explained. “CAR T therapy targets the tumor cells without hurting normal tissue.”

CAR T might also be preferable to other targeted approaches like antibody therapy.

“With antibodies, you need to continuously infuse them because they clear from the body very quickly,” she said. “But CAR T cells can persist in the patient for years. A single CAR T cell infusion can clear the tumor, and when a new tumor comes, the CAR T cells can ‘conquer’ it.”

Wang is also working on CAR technology to fight other types of cancers.

Her latest publication, the cover story in the latest issue of Clinical Cancer Research, focuses on multiple myeloma, a cancer of the plasma cells that produce antibodies in the blood. Wang and her colleagues developed a novel therapy that reprograms a patient’s T cells to recognize a specific protein found on the surface of myeloma cells — and then destroy those cells. This form of CAR T cell therapy is currently in preparation for submission to the Food and Drug Administration, with clinical trials expected to begin in June 2018.  

For Wang, whose driving passion is to end to the suffering she saw as a physician, her long hours in the lab are truly a joy.

“Every day, I have a new discovery,” she said. “And I just feel amazing when I see a patient have complete remission. That’s the best thing for me.”
 
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