Aspirin Powers New “Switchable” Cancer Immunotherapy
A new cancer treatment strategy, dubbed SAMBA, leverages the readily available and inexpensive drug salicylic acid – the active ingredient in aspirin – too precisely control the activity of engineered immune cells, offering a perhaps safer and more effective approach to fighting blood cancers like acute lymphoblastic leukemia and B cell lymphoma. Blood cancers represent roughly 10% of all new cancer diagnoses annually.
Conventional immunotherapy utilizes the body’s own immune system to target and destroy cancer cells, a practice dating back to 1891 with its initial use in bone cancer treatment. However, innovations like SAMBA aim to refine this approach, improving both safety and efficacy.
The core of SAMBA technology lies in engineering CAR T cells – immune cells modified to recognize and attack cancer – with a unique “switch.” This switch is activated by the presence of salicylic acid and deactivated when the drug is withheld. Laboratory testing demonstrated that SAMBA-equipped CAR T cells only eliminated cancer cells when salicylic acid was present.Removing the drug halted the immune response, providing a crucial safety mechanism absent in conventional CAR T cell therapy.
“We’re aiming for a rapid and controllable switch, much like a Transformer toy, to precisely direct the behavior of immune cells,” explains researcher Zhou. The process involves extracting CAR T cells from a patient,genetically modifying them with the SAMBA system,and then re-infusing them. Without salicylic acid, these engineered cells remain inactive, but the drug’s presence triggers their cancer-fighting capabilities.
Research indicates that combining SAMBA-engineered CAR T cells with salicylic acid yields the most promising results. Tumors exhibited greater shrinkage, and subjects experienced extended survival rates. Importantly, this approach considerably reduced the incidence of cytokine release syndrome (CRS), a dangerous and often life-threatening immune overreaction common in existing CAR T cell therapies. CRS occurs when excessive T cell activation leads to an uncontrolled release of inflammatory molecules.
“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 clarifies. ”By incorporating a switch, we can modulate activity and minimize risk. Should CRS occur, we can simply withdraw the drug and deactivate the circuit, as the system is conditionally active.”
While not a guaranteed cure, the research team reports that SAMBA demonstrated substantial improvements in treatment outcomes and represents a significant advancement in cancer therapy. They are optimistic about expanding the submission of this method beyond blood cancers in the future.
“SAMBA’s adaptable design offers a versatile platform for enhancing control and safety in both cell- and antibody-based therapies, potentially extending its use to a wider range of diseases,” states Huang.
The findings have been published in nature Chemical Biology, and the team has filed a US patent application for commercialization. To foster wider research and collaboration, the necessary reagents have been made available to academic researchers. The work was supported by grants from the National Institutes of Health and the Cancer prevention and Research Institute of Texas (CPRIT).
