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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Jin Xie, 2024. "Calcium nanoparticles target and activate T cells to enhance anti-tumor function," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54402-y
    DOI: 10.1038/s41467-024-54402-y
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    References listed on IDEAS

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    1. Miriam Y. Kim & Reyka Jayasinghe & Jessica M. Devenport & Julie K. Ritchey & Michael P. Rettig & Julie O’Neal & Karl W. Staser & Krista M. Kennerly & Alun J. Carter & Feng Gao & Byung Ha Lee & Matthew, 2022. "A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
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