Novel non-immunogenic trained immunity inducing small molecule with improved anti-tumor properties
Abstract Trained immunity refers to the non-specific innate immune memory response triggered by the epigenetic and metabolic rewiring of innate immune cells. A strengthened innate immune system significantly improves disease resistance. However, very few trained immunity-inducing molecules have been identified. Almost all molecules for training are primarily immunogenic and then subsequently induce training. Non-immunogenic molecules that induce training could be employed in therapies without the concern of adverse inflammatory reactions. We identified a small molecule, A1155463, that modulates cellular metabolism to induce trained immunity in macrophagesin-vitro. We show that nanomolar concentrations of these compounds uniquely alter only cellular metabolism without leading to apoptosis. We further observed that these compounds could induce training in anin-vivomodel in mice. A1155463 training improved anti-tumor resistance to B16.F10 melanoma cells. The effect was enhanced upon combination with checkpoint therapy. In summary, we report the discovery of a novel trained immunity-inducing small molecule with enhanced anti-tumor properties..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 29. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ajit, Jainu [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.03.22.585780 |
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| PPN (Katalog-ID): |
XBI043072216 |
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| 520 | |a Abstract Trained immunity refers to the non-specific innate immune memory response triggered by the epigenetic and metabolic rewiring of innate immune cells. A strengthened innate immune system significantly improves disease resistance. However, very few trained immunity-inducing molecules have been identified. Almost all molecules for training are primarily immunogenic and then subsequently induce training. Non-immunogenic molecules that induce training could be employed in therapies without the concern of adverse inflammatory reactions. We identified a small molecule, A1155463, that modulates cellular metabolism to induce trained immunity in macrophagesin-vitro. We show that nanomolar concentrations of these compounds uniquely alter only cellular metabolism without leading to apoptosis. We further observed that these compounds could induce training in anin-vivomodel in mice. A1155463 training improved anti-tumor resistance to B16.F10 melanoma cells. The effect was enhanced upon combination with checkpoint therapy. In summary, we report the discovery of a novel trained immunity-inducing small molecule with enhanced anti-tumor properties. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Knight, Hannah Riley |4 aut | |
| 700 | 1 | |a Chen, Qing |4 aut | |
| 700 | 1 | |a Solanki, Ani |4 aut | |
| 700 | 1 | |a Shen, Jingjing |4 aut | |
| 700 | 1 | |a Kahn, Aaron P. Esser |0 (orcid)0000-0003-1273-0951 |4 aut | |
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