Cell Engineering to Treat Cancer and Other Disease
Researchers at Gladstone Institutes and UC San Francisco have developed a strategy and molecular building blocks for the design of therapeutic cells with improved specificity and safety, and for the eventual customization of cell-based therapies.
Engineered immune cells can be precise and sophisticated in their ability to detect and eliminate cancer cells. But therapies based on engineered immune cells still face important limitations, including toxicity and the possibility that they could attack healthy cells. In addition, customizing existing therapeutic cells for new applications has been challenging.
"We have identified principles that should greatly facilitate the engineering of therapeutic cells with greater sensitivity, accuracy, and safety than was possible before," says research leader Kole Roybal in a press release issued by Gladstone Institutes. "Our work will provide biomedical researchers with a toolkit for directing a range of cell-based therapies to their intended targets and for programming their therapeutic activities."
"These smart cell therapies can unleash potent therapeutic activity precisely at the site of disease, improving the efficacy of the therapy and reducing the chance of life-threatening toxicities seen in patients," adds Roybal.
Therapeutic cells are covered with large proteins called receptors. The outer portion of a receptor recognizes a specific target (for instance a protein on the surface of a cancer cell) and the inner portion tells the therapeutic cell what to do upon recognizing this target. Previously the researchers had developed a receptor called synNotch that can direct therapeutic cells to better recognize and kill solid tumors.
Now there's a paper published in Cell. It describes how the researchers have improved the original synNotch by systematically swapping various portions of the receptor. Eventually, the researchers have produced a catalog of receptors dubbed SNIPRs, which are small enough for cost-effective engineering into human cells.
"A challenging but fun feat was figuring out how different parts of known receptors function, so that we could take those pieces apart and put them back together in novel ways to meet our design specifications," says researcher Raymond Liu. "Understanding the rules of receptor design allowed us to build receptors that are more effective and also better suited for clinical translation," adds researcher Iowis Zhu.
Roybal co-founded a company called Arsenal Bio. It is participating in the development of cell therapies based on SNIPRs for various types of cancer, as well as autoimmune diseases.
"Engineered cells have the potential to operate as much smarter therapeutics than traditional small molecules and biologics," concludes Roybal. "We're hoping our new receptor system will serve as a technology platform enabling scientists and clinicians to design safer, targeted, and more effective cell-based therapies against cancer and many other diseases."
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