Dendritic cell vaccine with mRNA targeted to the proteasome by polyubiquitination

Biochemical and Biophysical Research Communications
Akihiro HosoiKazuhiro Kakimi

Abstract

Dendritic cells (DCs) transfected with mRNA encoding tumor-associated antigens (TAAs) can induce tumor-specific T-cell responses. To potentiate this, we transfected mature DCs (mDCs) with mRNA encoding TAA targeted to the proteasome. DCs were generated from bone marrow cells by culture with 20 ng/ml GM-CSF and maturation with 1 microg/ml LPS. These mDCs were then electroporated with 10 microg of mRNA. Antigen presentation after electroporation with in vitro transcribed mRNA was compared with mRNA from a construct of the TAA preceded by ubiquitin. Proteasomal targeting of mRNA encoding cotranslationally ubiquitinated antigen was found to enhance intracellular degradation of target protein, and result in more efficient priming and expansion of TAA-specific CD8(+) T-cells. We therefore suggest that RNA-transfected DC vaccine efficacy could be improved by the use of mRNA targeted to the proteasome.

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Citations

Apr 19, 2011·Current Opinion in Immunology·Sebastian KreiterUgur Sahin
Oct 18, 2016·Cytotherapy·Rebecca S Abraham, Duane A Mitchell
Aug 9, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ligong LuYou-Wen He

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