USC researchers have developed a new CAR T-cell system that’s more effective against breast, prostate and other solid tumor cancers. (Image/Midjourney)
Every year, millions of people are diagnosed with solid tumor cancers, including breast, prostate, lung and brain. For most, one of medicine’s most powerful new tools, CAR T-cell therapy, remains largely ineffective. The therapy has produced remarkable results in blood cancers such as leukemia and lymphoma, but solid tumors are a different, far more stubborn problem.
A team of USC engineers aims to change that.
Their new CAR T-cell system addresses three of the biggest challenges that have limited the therapy’s effectiveness against solid tumors: it can be redirected to new targets at any point; activates only at the tumor site to protect healthy tissue; and can train itself to attack cancers it was not originally designed to fight.
Together, these advances point to a significant step forward in cancer treatment.
“Before this approach, we had never seen something that gives CAR T cells this kind of programmability while also achieving a very safe performance,” said Ziliang Huang, a research scientist at USC’s Alfred E. Mann Department of Biomedical Engineering, co-lead author of a recent study and now an associate professor of biomedical engineering at Chongqing Medical University. “That combination is what makes this genuinely new and exciting.”
The findings were published in “Nature Communications” in a paper titled “Engineering Programmable CAR and Antigen Pairing via Drug-gated Light Activation.” In addition to Huang, co-authors include USC Viterbi’s Yingxiao Peter Wang, the Dwight C. and Hildagarde E. Baum Chair in Biomedical Engineering and department chair; Longwei Liu, an assistant professor of ophthalmology and biomedical engineering; doctoral student Tianze Guo; doctoral student Yuxuan Wang; postdoctoral researcher Linshan Zhu; alumnus Zhuohang Wu; and Praopim Limsakul, Yiqian Wu and Molly Allen of the University of California, San Diego.
A therapy that can change course
CAR T therapy begins with a patient’s own immune cells. Doctors extract T cells, the immune system’s front-line defenders, and engineer them in a lab to recognize a specific marker on cancer cells. The result is a targeted treatment: once reinfused, the cells hunt down and destroy anything bearing that marker.
In blood cancers, this approach works well because tumor cells are relatively uniform and easier to identify. Solid tumors are more complex: they are embedded in tissue, prone to genetic changes and capable of evolving to shed the markers the T cells are trained to find. When that happens, the therapy stops working.
“CAR T is very powerful, but it’s not always precise or controllable,” said Yingxiao Peter Wang, who has spent more than a decade developing immune cell therapies. “Once these cells are active, they don’t always stay where you need them.”
The USC team’s solution was to make the therapy adaptable. Instead of hardwiring each T cell to a single target, they designed a system that uses a matching antibody as a guide. The antibody directs the T cells to whatever tumor marker doctors want to attack; changing targets is easy.
“You can design which target you want, whenever you want,” Wang said. “You can even switch targets mid-treatment if the tumor tries to escape.”
Turning the therapy on, only where it’s needed
A therapy that can target many markers raises a key concern: What if those same markers appear on healthy cells?
The researchers addressed this with a two-step activation system; both steps are required to turn the therapy on.
First, patients take tamoxifen, a drug already used in cancer care, which partially primes the CAR T cells. But the cells cannot fully activate on their own; they need a second trigger, a pulse of blue light directed at the tumor. Only cells that receive both signals become active. Cells that move away from the tumor do not receive the light signal and remain dormant, sparing healthy tissue.
In laboratory studies, this approach reduced damage to healthy tissue by more than 90% compared with standard CAR T treatment; a safety improvement that could expand the therapy to patients who cannot currently tolerate it.
In models of aggressive breast and prostate cancers, two of the most difficult solid tumors to treat, the system produced strong tumor suppression with no meaningful damage to surrounding tissue.
The light-based system also helps solve another major challenge: identifying where to attack. Because many solid tumors resemble healthy tissue, the researchers engineered a way to make cancer cells reveal themselves.
When exposed to light, a small number of tumor cells produce a “synthetic flag,” a signal that attracts and trains CAR T cells. Once the immune cells arrive and bind to this artificial target, they spread through the tumor.
“We essentially hijack the tumor’s own machinery to make it visible,” Wang said. “Once the CAR T cells are activated, they move through the surrounding area and eliminate the cancer.”
Fighting other cancers
The team is now refining how the therapy is delivered and testing it across a wider range of cancers. Wang said researchers are in discussions with clinical partners about early-phase human trials and are working through the regulatory steps required to move forward. Huang said human testing could begin within five years.
“In the next five to 10 years, we want these methods to help patients fight solid tumors with better outcomes,” Wang said. “Whatever technology we develop in the lab, the goal is always to get it to patients. That’s what drives this work.”
Published on June 16th, 2026
Last updated on June 16th, 2026