| First Author | Yang W | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 10095 |
| PubMed ID | 39572569 | Mgi Jnum | J:371366 |
| Mgi Id | MGI:7784562 | Doi | 10.1038/s41467-024-54402-y |
| Citation | Yang W, et al. (2024) Calcium nanoparticles target and activate T cells to enhance anti-tumor function. Nat Commun 15(1):10095 |
| abstractText | Calcium signaling plays a crucial role in the activation of T lymphocytes. However, modulating calcium levels to control T cell activation in vivo remains a challenge. In this study, we investigate T cell activation using 12-myristate 13-acetate (PMA)-encapsulated CaCO(3) nanoparticles. We find that anti-PD-1 antibody-conjugated CaCO(3) nanoparticles can be internalized by T cells via receptor-mediated endocytosis and then gradually release calcium. This results in an increase in cytosolic calcium, which triggers the activation of NFAT and NF-kappaB pathways, especially when the surface of the CaCO(3) nanoparticles is loaded with PMA. Animal studies demonstrate that the PMA-loaded calcium nanoparticles enhance the activation and proliferation of cytotoxic T cells, leading to improved tumor suppression without additional toxicity. When tested in metastatic tumor models, T cells loaded with the calcium nanoparticles prior to adoptive cell transfer control tumor growth better, resulting in prolonged animal survival. Our approach offers an alternative T cell activation strategy to potentiate immunotherapy by targeting a fundamental signaling pathway. |
