Induction of antigen-specific CD8+ cytotoxic T cells by dendritic cells co-electroporated with a dsRNA analogue and tumor antigen mRNA

Gene Therapy
Annelies MichielsJ L Aerts

Abstract

The maturation state of dendritic cells (DCs) is an important determinant for the initiation and regulation of adaptive immune responses. In this study, we wanted to assess whether functional activation of human monocyte-derived DCs can be achieved by electroporation of an activation signal in the form of double-stranded (ds) RNA and whether simultaneous electroporation of the dsRNA with tumor antigen encoding mRNA can lead to the induction of a cytotoxic T-lymphocyte (CTL) response. Electroporation of immature DCs with poly(I:C(12)U), a dsRNA analogue, resulted in phenotypic as well as functional changes, indicative of DC maturation. Co-electroporation of DCs with both poly(I:C(12)U) and Melan-A/MART-1 encoding mRNA induced strong anti-Melan-A/MART-1 CD8(+) T-cell responses in vitro. Higher numbers of Melan-A/MART-1-specific CTLs were consistently obtained with poly(I:C(12)U)-activated DCs compared to DCs matured in the presence of an inflammatory cytokine cocktail. These results indicate that DC co-electroporation with both dsRNA and tumor antigen encoding mRNA induces fully activated and antigen-loaded DCs that promote antigen-specific CTL responses and may provide the basis for future immunotherapeutic strategies.

References

Jan 1, 1989·Cold Spring Harbor Symposia on Quantitative Biology·C A Janeway
Oct 6, 1998·Annual Review of Biochemistry·G R StarkR D Schreiber
Mar 2, 1999·The Journal of Experimental Medicine·M CellaA Lanzavecchia
Nov 5, 1999·Nature Medicine·S GallucciP Matzinger
Aug 30, 2001·Nature Immunology·T HorngR Medzhitov
Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Esther C de JongMartien L Kapsenberg
Aug 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter PonsaertsViggo F I Van Tendeloo
Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Misako MatsumotoTsukasa Seya
Dec 4, 2003·Nature Reviews. Immunology·Martien L Kapsenberg
Jan 22, 2004·Current Opinion in Immunology·Caetano Reis e Sousa
Jul 26, 2005·Immunity·Hiroki KatoShizuo Akira

❮ Previous
Next ❯

Citations

May 16, 2007·Cancer Immunology, Immunotherapy : CII·Sandra TuyaertsAude Bonehill
Apr 24, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aude BonehillKris Thielemans
Jul 16, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Rémi J CreusotC Garrison Fathman
Mar 1, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·An M T Van NuffelAude Bonehill
Jul 20, 2010·Immunotherapy·Elzbieta Pajtasz-Piasecka, Marie Indrová
Jan 12, 2013·Vaccine·Neeraj Kumar GargRajeev K Tyagi
Dec 20, 2008·Journal of Internal Medicine·C R Rinaldo
Oct 19, 2007·Cytotherapy·D L DiGiusto, L J N Cooper
Jan 8, 2013·Human Vaccines & Immunotherapeutics·Sandra Van LintKarine Breckpot
Aug 9, 2019·Immunotherapy·Aishwarya JoshiRajeev K Tyagi
Jan 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karine BreckpotKris Thielemans
Oct 5, 2018·Cancer Immunology, Immunotherapy : CII·Michele TomasicchioKeertan Dheda
Aug 9, 2017·Journal of Immunology Research·J M J Van den BerghE Lion
Apr 3, 2020·Current Opinion in Biotechnology·Rita AhmedLana E Kandalaft
Jul 16, 2021·Frontiers in Cell and Developmental Biology·Ahmed SalahYuehong Wu

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.