Researchers from the University of California Los Angeles (UCLA) and Stanford Medicine announced on Mar. 20 that they have developed a new class of engineered T cells designed to more effectively target and destroy prostate cancer cells. The team collaborated with scientists from the University of Utah and Columbia University, working within the Parker Institute for Cancer Immunotherapy network.
The development is significant because it could lead to safer and more effective immunotherapies for prostate cancer, a disease where current treatments sometimes struggle to distinguish between healthy tissue and tumors. The research centers on enhancing T cell receptor (TCR) therapy by introducing a natural “catch bond”—a fishhook-like interaction that strengthens when immune cells pull against each other—allowing T cells to better recognize and attack tumor cells without harming healthy tissue.
“By engineering catch bonds, we aim to benefit more patients by overcoming immune tolerance,” said Dr. Owen N. Witte, co-senior author of the study and member of the UCLA Health Jonsson Comprehensive Cancer Center. Dr. K. Christopher Garcia, also a co-senior author from Stanford School of Medicine, said, “In our collaborative work, we demonstrate that just a single amino acid change introducing these ‘fishhooks’ is sufficient to transform immune cells into a potent killer mode.”
The researchers focused on fine-tuning naturally occurring T cell receptors so they could better recognize prostatic acid phosphatase (PAP), a protein commonly found in prostate tumors. Using catch bond engineering—a technique developed at Stanford—they altered one or two amino acids in the receptor, creating versions that were stronger at binding tumor targets while maintaining specificity for cancerous tissue. Laboratory tests showed these engineered T cells had longer contact with cancer cells, released more tumor-killing molecules such as Granzyme B and IFNγ, proliferated better, and resisted exhaustion compared to unmodified T cells.
Dr. Xiaojing Tina Chen, co-first author from Stanford School of Medicine, said: “Using advanced structural studies at atomic resolution, we were able to demonstrate how a tiny change… can extend the bond lifetime, dramatically boosting the T cell’s ability to kill tumors in living models.” Dr. Zhiyuan Mao from UCLA added: “This work shows that tumor control can be linked to a single molecular bond.”
The findings suggest catch bond engineering may offer a general strategy for improving adoptive cell therapies across various cancers. Garcia said: “These findings suggest that catch bond engineering could be a generalizable strategy to enhance T cell therapies for many cancers.” Witte added: “By creating T cells that are stronger, longer-lasting, and highly precise, the approach moves the field closer to safer and more effective adoptive cell therapies for patients.”
UCLA has been associated with notable figures such as Nobel laureates and MacArthur Fellows according to its official website. The university operates within the University of California system according to its official website and features a 419-acre campus supporting academic and research activities according to its official website. UCLA fosters diverse perspectives through its academic programs according to its official website and has gained national acclaim through achievements in scholarship, arts, athletics—and research like this recent study.