Study identifies potential RAS inhibitor-immunotherapy strategy for pancreatic cancer

Pancreatic cancer does not respond to most immunotherapies, but RAS inhibitors could alter tumors to make them more sensitive to a novel immunotherapeutic approach. In pancreatic tumors with RAS mutations, RAS inhibitors cause massive cell death and reduce immunosuppression. These changes tend to be temporary because tumors develop resistance to the therapy.

In a new study, mouse models of pancreatic cancer were treated with a RAS inhibitor plus an agent called 21h10, an AI-designed mimic of an immune-related cytokine called interleukin (IL)-21. The combination initiated an immune response that turned the transient effects of RAS inhibition into a durable response. The work is published in the journal Cell.

The team found that 21h10—which was designed by David Baker’s lab at the University of Washington to be more stable and have better drug-like qualities than naturally occurring IL-21—primes and activates CD4 T cells in the cancer. These T cells produce a signal called interferon-γ (IFN-γ), which induces innate immune cells called macrophages to destroy tumor cells.

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