New Compounds Boost T Cell Production, Offering Potential for Immunotherapies
Boston, MA – September 2, 2025 – Researchers have identified a new class of soluble Notch agonists capable of dramatically increasing T cell production in the lab, a breakthrough that could pave the way for more effective immunotherapies against cancer, autoimmune diseases, and infectious illnesses. Published today in Nature, the study details how these compounds stimulate the development of T cells – critical components of the immune system – without requiring direct cell-to-cell contact, a limitation of current Notch-based therapies.
The findings address a longstanding challenge in harnessing the power of the Notch signaling pathway, a crucial regulator of T cell development.Existing approaches often rely on activating Notch receptors through interactions with cells on their surface. This new research demonstrates that soluble agonists can bypass this requirement, offering a potentially simpler and more scalable method for boosting T cell numbers. This is especially significant as T cell deficiencies are central to many diseases, and expanding T cell populations ex vivo for adoptive cell therapy is frequently enough hampered by limited expansion capacity.
The research team,led by scientists at Harvard Medical School,engineered soluble ligands that bind to Notch receptors on T cell precursors,triggering the signaling cascade that drives their differentiation and proliferation. These agonists demonstrated a significant increase in T cell production in laboratory settings. The team observed a robust expansion of both CD4+ helper T cells and CD8+ cytotoxic T cells, the latter of which are particularly significant for directly killing cancer cells and virus-infected cells.
“This is a fundamentally new way to activate Notch signaling in T cells,” explained a researcher involved in the study. “By delivering the signal directly, we can overcome many of the barriers that have hindered previous attempts to leverage this pathway for therapeutic benefit.”
The researchers are now focused on optimizing the compounds for in vivo use and evaluating their efficacy in animal models of disease. Further studies will be needed to assess the safety and potential side effects of these soluble Notch agonists before they can be tested in human clinical trials. Though, the initial results suggest a promising new avenue for developing targeted immunotherapies with the potential to revolutionize the treatment of a wide range of conditions.
doi: https://doi.org/10.1038/d41573-025-00143-6
