New research repurposes ancient remedy for blood cancer treatment

Two millennia after Hippocrates used willow bark to ease pain and fever, researchers at the Texas A&M University Health Science Center (Texas A&M Health) have transformed its key ingredient—salicylic acid—into a molecular “remote control” that can turn therapeutic cell functions on or off.

In a recent study, Yubin Zhou, MD, PhD, FAIMBE, and Yun Huang, PhD, with the Texas A&M Health Institute of Biosciences and Technology used this technology—called Salicylic Acid-Mediated Binary Association (SAMBA)—to combat two common blood cancers: acute lymphoblastic leukemia and B cell lymphoma. Blood cancers account for approximately 10% of new cancer diagnoses each year.

SAMBA uses salicylic acid, or aspirin, which is a cost-efficient and widely available drug for therapeutic use, making it a promising alternative to more complex or expensive forms of cancer immunotherapy.

Immunotherapy—which uses the body’s own immune system to seek out and kill cancer cells—has been used since 1891 for bone cancer. But innovations like SAMBA are helping researchers make it safer and more effective.

SAMBA technology works by engineering CAR T cells so their cancer-killing activity can be turned on or off simply by giving or withholding salicylic acid, allowing doctors to precisely control when the treatment is active. In laboratory studies, SAMBA-equipped CAR T cells only destroyed cancer cells when salicylic acid was present. Stopping the salicylic acid “switch” caused the immune cells to pause their attack, offering a new safety layer over traditional CAR T cell therapy.

“Much like playing with a Transformer toy, where you can quickly flip between a car and a robot, we’re trying to recreate that quick switch so we can better control the immune cells and make them behave the way we want them to behave,” Zhou said. “We developed a few tools over the last few years and engineered the elements into immune cells. You take the CAR T cells from the patient, then you engineer them, teach them new tricks and infuse them back into the patient. Once they are infused, without SAMBA they are non-functional, but using the SAMBA system and the aspirin, you can switch it on and off once the drug is being metabolized.”

The research showed treatment with the SAMBA-engineered CAR T cells and salicylic acid provided the best outcomes. The tumors shrank the most with this combination, and subjects experienced longer survival. Unlike other CAR T treatments, this approach reduced dangerous immune overreactions known as cytokine release syndrome—a common and serious side effect in current therapies—by creating and activating circuits, similarly to how light switches work.

“Cytokine storm, or cytokine release syndrome, can occur when excessive activation of T cells triggers uncontrolled production and release of pro-inflammatory cytokines, which can lead to life-threatening toxicity,” Zhou said. “But if you can put a switch there, you can slow it down and fine tune the activity to reduce the risk. If cytokine storm does happen, we can withdraw the drug and close the circuit, since it is conditionally active.”

Although the treatment is not 100% successful, the researchers said SAMBA showed significant improvements in outcomes and showcases a significant breakthrough in cancer treatment. The are hopeful this method can be expanded beyond blood cancers in the future.

“Looking ahead, SAMBA’s modular architecture provides a flexible framework for improving control and safety in both cell- and antibody-based therapies, with the potential to extend its use beyond blood cancers to other disease settings,” Huang said.

The team has filed a U.S. patent application for commercialization and made the reagents available to academic researchers to encourage broader use and collaboration. This work is supported by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas (CPRIT).