Armed with $49.5 million in its first formal round of funding, Obsidian Therapeutics has launched to fine-tune the activity of cellular and gene therapies. The Boston-based biotech firm aims to make the treatments safer and more effective across a broader range of diseases.
Ever since early clinical trials suggested chimeric antigen receptor (CAR) T cells could quickly obliterate blood cancer in some patients, companies have been racing to harness the technology, in which a patient’s own T cells are genetically engineered to include a protein receptor that helps them see and attack cancer cells.
The problem is that CAR T cells “are sort of on a therapeutic knife edge: They can either be profoundly effective or terribly toxic,” says Obsidian CEO Michael Gilman.
When CAR T cells home in on cancer cells, they can prompt a rapid—and potentially deadly—release of cytokines, proteins involved in immune system response. Moreover, CAR T cells don’t always produce lasting responses.
Obsidian hopes its technology, which was discovered in the labs of Stanford University professor Thomas Wandless, can address those limitations.
Wandless found a way to add a region on a protein, what he calls a “destabilizing domain,” that allows expression of the protein to be controlled based on exposure to a small molecule. Without the small molecule around, the protein is tagged for disposal in the cellular trash bin; when the small molecule—an already-approved drug—is given, the protein is stabilized.
By giving proteins something like a volume knob that can be tuned by small molecules, Obsidian expects to avoid the sometimes-deadly cytokine storms, while also giving CAR T cells “entirely new functionalities,” Gilman says.