Calcium nanoparticles target and activate T cells to enhance anti-tumor function

Wei Yang, Zhizi Feng, Xinning Lai, Jianwen Li, Zhengwei Cao, Fangchao Jiang, Fanghui Chen, Shuyue Zhan, Feng Kong, Li Yang, Yong Teng, Wendy T. Watford, Gang Zhou () and Jin Xie ()
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Wei Yang: University of Georgia
Zhizi Feng: University of Georgia
Xinning Lai: University of Georgia
Jianwen Li: University of Georgia
Zhengwei Cao: University of Georgia
Fangchao Jiang: University of Georgia
Fanghui Chen: Emory University School of Medicine
Shuyue Zhan: University of Georgia
Feng Kong: University of Georgia
Li Yang: University of Georgia
Yong Teng: Emory University School of Medicine
Wendy T. Watford: University of Georgia
Gang Zhou: Medical College of Georgia
Jin Xie: University of Georgia

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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 CaCO3 nanoparticles. We find that anti-PD-1 antibody-conjugated CaCO3 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-κB pathways, especially when the surface of the CaCO3 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.

Date: 2024
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DOI: 10.1038/s41467-024-54402-y

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