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In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo

Author

Listed:
  • N. N. Parayath

    (Fred Hutchinson Cancer Research Center)

  • S. B. Stephan

    (Fred Hutchinson Cancer Research Center)

  • A. L. Koehne

    (Fred Hutchinson Cancer Research Center)

  • P. S. Nelson

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • M. T. Stephan

    (Fred Hutchinson Cancer Research Center
    University of Washington
    University of Washington)

Abstract

Engineering chimeric antigen receptors (CAR) or T cell receptors (TCR) helps create disease-specific T cells for targeted therapy, but the cost and rigor associated with manufacturing engineered T cells ex vivo can be prohibitive, so programing T cells in vivo may be a viable alternative. Here we report an injectable nanocarrier that delivers in vitro-transcribed (IVT) CAR or TCR mRNA for transiently reprograming of circulating T cells to recognize disease-relevant antigens. In mouse models of human leukemia, prostate cancer and hepatitis B-induced hepatocellular carcinoma, repeated infusions of these polymer nanocarriers induce sufficient host T cells expressing tumor-specific CARs or virus-specific TCRs to cause disease regression at levels similar to bolus infusions of ex vivo engineered lymphocytes. Given their ease of manufacturing, distribution and administration, these nanocarriers, and the associated platforms, could become a therapeutic for a wide range of diseases.

Suggested Citation

  • N. N. Parayath & S. B. Stephan & A. L. Koehne & P. S. Nelson & M. T. Stephan, 2020. "In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19486-2
    DOI: 10.1038/s41467-020-19486-2
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    Cited by:

    1. Zhijian Li & Laura Amaya & Ruoxi Pi & Sean K. Wang & Alok Ranjan & Robert M. Waymouth & Catherine A. Blish & Howard Y. Chang & Paul A. Wender, 2023. "Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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