A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8+ T Cells

Regine J. Dress, William W. Ho, Victor Ho, Jian Hang Lam, Fabien M. Décaillot, Gaurav Sinsinbar, Jenetta Soo, Gowshika Rengasamy, Amit Kumar Khan, Thomas Andrew Cornell, Teck Wan Chia, Shrinivas Venkataraman, Madhavan Nallani, Florent Ginhoux

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    Cancer is one of the leading causes of death worldwide. In recent years, immune checkpoint inhibitor therapies, in addition to standard immuno- or chemotherapy and surgical approaches, have massively improved the outcome for cancer patients. However, these therapies have their limitations and improved strategies, including access to reliable cancer vaccines, are needed. Here, we describe the use of self-assembling artificial cell membrane (ACM) polymersomes to deliver tumour-specific peptides to trigger sustainable and efficient anti-tumour immune responses. We found that ACM polymersomes were highly efficient in targeting and activating mononuclear phagocytes (MNP) including dendritic cells (DC), while providing long-term reservoirs of antigens for continued immune cell priming. Subcutaneous injection of ACM-encapsulated tumour-antigen-peptides into tumour-bearing mice resulted in improved priming of CD8+ T cells and increased generation of tumour-antigen-peptide specific CD8+ effector T cells. Prophylactic and therapeutic immunisation with ACM-encapsulated peptides resulted in changes to the MNP composition in the tumour microenvironment, tumour regression and improved survival of immunised mice. Combining anti-PD-1 immune checkpoint inhibitor therapy with ACM polymersome peptide delivery further boosted anti-tumour immunity. Our results show that ACM polymersome nanocarriers efficiently instruct anti-tumour immune responses offering a promising new approach for vaccination and cancer immunotherapy. Trial Registration: NCT05385991.

    langue originaleAnglais
    journalImmunology
    Les DOIs
    étatAccepté/sous presse - 1 janv. 2025

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