A team of researchers led by scientists from Harvard Medical School and Boston Children’s Hospital has harnessed AI to design synthetic proteins that activate a key immune pathway. This is aimed at enabling large-scale generation of T cells.
The research shows how AI-powered protein engineering could unlock new possibilities in cancer treatment and vaccine development.
At the core of this innovation is the Notch signalling pathway, a critical cellular mechanism that governs immune cell development, especially the formation of T cells from progenitor cells.
While the body needs a surge of T cells to fight cancers and viral infections, activating this pathway has been a long-standing challenge due to the lack of effective molecular activators.
To address this, the researchers employed AI-driven protein design. The same approach won scientists David Baker, Demis Hassabis and John Jumper the 2024 Nobel Prize in Chemistry. Using these tools, the team created a library of custom-designed soluble Notch agonists and tested their ability to trigger T cell development.
George Daley, dean of Harvard Medical School, and his team, including lead author and research fellow at Boston Children’s Hospital, Rubul Mout, who previously worked with Nobel laureate David Baker, utilised the Rosetta software platform developed in the Baker Lab.
Mout explained that previous attempts to activate Notch signalling relied on methods not viable in live organisms. The AI-designed soluble agonists, by contrast, work inside living systems and can be administered as part of therapeutic processes.
When tested in a lab bioreactor, these synthetic proteins led to large-scale production of T cells, a significant advancement for chimeric antigen receptor (CAR) T cell therapies, which require mass immune cell generation.
In animal studies, the agonists enhanced vaccine responses and led to the formation of memory T cells, suggesting strong potential for long-term immunity.
“This technology allows us to engineer proteins that not only generate T cells but also enhance their cancer-killing ability,” Mout reportedly said. “It opens up opportunities in immunotherapy, vaccine development and immune cell regeneration.”
The project involved 24 researchers, including Daley and collaborators from the Karolinska Institute and Dana-Farber Cancer Institute.
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