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Tumour antigen spreading mediated by vaccine-boosted CAR T cells

Nature Reviews Immunology volume 23, page 7 (2023)Cite this article

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Loss of the targeted antigen is a major obstacle to the success of therapy with chimeric antigen receptor (CAR) T cells, particularly for solid tumours. Antigen spreading (expansion of the immune response to secondary epitopes) to prime endogenous T cells against non-CAR-targeted tumour antigens could overcome this limitation and ensure long-lasting effects of CAR T cell therapies. However, the mechanism of antigen spreading in CAR T cell therapy remains poorly understood.

In 2019, Ma et al. reported a vaccine-boosted CAR T cell approach that made use of a phospholipid polymer attached to the target antigen of the CAR (amph-ligand) in a tumour model. When injected, this amph-ligand integrates into the membrane of dendritic cells (DCs) in lymph nodes and promotes DC interactions with CAR T cells, resulting in improved anti-tumoural effect.

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References

Original article

  • Ma, L. et al. Eradication of tumors with pre-existing antigenic heterogeneity by vaccine-mediated co-engagement of CAR T and endogenous T-cells. Preprint at bioRxiv https://doi.org/10.1101/2022.10.05.511036 (2022)

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  1. Preprint Club, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jaime Mateus-Tique & Brian Brown

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  1. Jaime Mateus-Tique
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  2. Brian Brown
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Correspondence to Jaime Mateus-Tique.

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Mateus-Tique, J., Brown, B. Tumour antigen spreading mediated by vaccine-boosted CAR T cells. Nat Rev Immunol 23, 7 (2023). https://doi.org/10.1038/s41577-022-00811-3

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  • DOI: https://doi.org/10.1038/s41577-022-00811-3

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