Transduction with a fiber-modified adenoviral vector is superior to non-viral nucleofection for expressing tumor-associated Ag mucin-1 in human DC

Cytotherapy
E B M van LeeuwenG M J Bos

Abstract

DC-presenting tumor Ag are currently being developed to be used as a vaccine in human cancer immunotherapy. To increase the chances for successful therapy it is important to deliver full-length tumor Ag instead of loading single peptides. Methodologically, several recombinant DNA delivery techniques have been used. In this study we compared nucleofection, an optimized form of electroporation, and adenoviral transduction regarding their efficiency to transduce human monocyte-derived (Mo-) DC in vitro. Expression of the tumor-associated Ag mucin-1 (MUC1) after adenoviral transduction (rAd5Fib35-MUC1) was determined using two MAb. We showed that the viability of cells and percentage of green fluorescent protein (GFP)-positive cells after transduction with a fiber-modified adenoviral vector (rAd5F35-GFP) was much higher than after nucleofection. Furthermore, phenotype and function of DC were not impaired by infection with adenovirus particles. Cells matured normally; up-regulation of CD40, CD80, CD83, CD86 and HLA-DR was not affected by adenoviral transduction. The capacity to stimulate naive T-cell proliferation was preserved and no change in IL-10 production was observed. Production of IL-12 increased up to 500-fold upon adenovir...Continue Reading

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Citations

May 20, 2008·Cancer Immunology, Immunotherapy : CII·Lazar VujanovicLisa H Butterfield
Mar 5, 2008·Journal of Immunotherapy·Lisa H ButterfieldAntoni Ribas
Sep 5, 2008·Expert Review of Vaccines·Choon-Kit TangVasso Apostolopoulos
Dec 20, 2008·Journal of Internal Medicine·C R Rinaldo
Sep 29, 2020·Expert Opinion on Drug Delivery·Aranit HarizajKevin Braeckmans

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