UCSF Team Develops Cellular Sensors for Targeted Cancer Therapy

UC San Francisco researchers have created a new class of customizable biological sensors that could revolutionize cancer treatment by enabling more precise and effective therapies with fewer side effects. The breakthrough, published in Nature, centers on engineered receptors called SNIPRs (synthetic intramembrane proteolysis receptors) that can detect specific molecules in a cell's environment and trigger targeted responses.

Building on their previous work with synNotch receptors, the team led by Kole Roybal has developed SNIPRs that can bind to soluble molecules around a cell. When activated, these receptors cluster together and interact with the cell's DNA, altering gene expression in customizable ways.

The researchers demonstrated the potential of SNIPRs by incorporating them into CAR-T cells, a type of immunotherapy used to fight cancer. The engineered cells were designed to activate only in the presence of specific immune molecules often found near tumors. In mouse studies, these SNIPR-equipped CAR-T cells effectively targeted and shrank tumors while minimizing damage to healthy tissue.

David Baker, a collaborator on the project, likened the system to "two-factor authentication for immunotherapy," as the cells must detect both the tumor environment and cancer cells before launching an immune response.

The versatility of SNIPRs suggests potential applications beyond cancer treatment, including therapies for autoimmune diseases. As Dr. Roybal noted, "We can now program a cell to localize to a site of disease and then carry out a very specific set of therapeutic tasks."