High-resolution microscopic images of T cells that have been engineered with TGF-beta SNIPRs (shown in red) as they bind to TGF-beta (shown in green). The SNIPRs activate once the receptors fold into the cell (shown in purple).
Most cancer treatments – from chemotherapies to engineered immune cells – have a host of side effects, in large part because they affect healthy cells in the body at the same time as targeting tumor cells. For the same reason, designing new cancer drugs can be challenging due to the molecular similarities between tumor cells and healthy cells.
Now, UC San Francisco researchers have designed highly customizable biological sensors that can ensure engineered cells are only activated in certain environments – such as the vicinity of a tumor. This could yield cancer therapies that are precisely delivered to tumors, making them more effective and giving them fewer side effects than today’s treatments. It also could lead to new, targeted therapies for other diseases.
The breakthrough, appearing in Nature on Nov. 14, revolves around engineered receptors on the surface of cells that can sense molecules in the surrounding environment and, in response, change the expression of genes inside the cells.
“We can now program a cell to localize to a site of disease and then carry out a very specific set of therapeutic tasks,” said Kole Roybal, PhD, a co-senior author of the new paper and an associate professor of microbiology and immunology at UCSF. “This is the culmination of more than a decade of work into the molecular details of these receptors and how they can be modified.”