Polyarginine-mediated protein delivery to dendritic cells presents antigen more efficiently onto MHC class I and class II and elicits superior antitumor immunity

The Journal of Investigative Dermatology
Hiroshi MitsuiShinji Shimada

Abstract

Protein transduction domains (PTDs) have been used increasingly to deliver reagents to a variety of cell types in vitro and in vivo. We have previously shown that HIV TAT-PTD-containing whole protein antigens (Ags)-transduced dendritic cells (DCs) stimulated Ag-specific CD8+ and CD4+ T cells. Although the cytotoxic T lymphocytes (CTL) activity generated was sufficient to prevent engraftment of mice with Ag-expressing tumors, treatment of tumor-bearing mice with TAT-PTD Ag-transduced DCs resulted in tumor regression in some animals. Recently, several other PTDs were reported to promote higher transduction efficiencies than TAT-PTD. To evaluate the role of individual PTDs in induction of immune responses in tumor vaccination studies, we engineered recombinant fusion Ovalbumin (OVA) that contained three differrent PTDs, including the most efficacious known PTD (polyarginine (R9)-PTD). Our results demonstrated that R9-PTD-containing OVA transduced DCs most efficiently, and that transduction efficacy was closely correlated with the extent of Ag-specific CD4+ and CD8+ T-cell activation in vitro and in vivo. Repeated vaccination with R9-PTD-OVA-transduced DC in (OVA-expressing) tumor-bearing mice induced enhanced antitumor immunity, a...Continue Reading

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Citations

Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Takashi NakamuraHideyoshi Harashima
Jan 11, 2011·Journal of Dermatological Science·Naotaka ShibagakiShinji Shimada
Jun 25, 2010·The Journal of Investigative Dermatology·Katharina KronenbergEsther von Stebut
Mar 7, 2018·Cellular and Molecular Life Sciences : CMLS·Morgan GrauMadiha Derouazi
Mar 5, 2016·Immune Network·Sangho LimJe-Min Choi
Oct 5, 2019·Expert Opinion on Drug Delivery·Kimia KardaniAzam Bolhassani
Sep 10, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michel LéonettiGervaise Moine
Nov 16, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuong D PhamMyung-Hee Kwon
Aug 5, 2010·Molecular Cancer Therapeutics·Takashi OkamotoShinji Shimada
Mar 24, 2021·Cancer Gene Therapy·Zeynab MarzhoseyniHamed Mirzaei
May 17, 2019·Molecular Pharmaceutics·Coralie M BacklundThomas L Andresen

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