HPV-E7 delivered by engineered exosomes elicits a protective CD8⁺ T cell-mediated immune response

Viruses
Paola Di BonitoM Federico

Abstract

We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These...Continue Reading

References

Apr 10, 1999·Advances in Anatomic Pathology·K J Busam, A A Jungbluth
Apr 26, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·S SparacioV Bosch
May 22, 2002·The Journal of Experimental Medicine·Giovanna AndreolaStefano Fais
Jul 26, 2003·Blood·Aude de GassartMichel Vidal
Dec 1, 1950·British Journal of Cancer·P A GORER
Jun 23, 2004·Nature Structural & Molecular Biology·John A G BriggsMarc C Johnson
Feb 23, 2005·Journal of Translational Medicine·Michael A MorseH Kim Lyerly
Aug 13, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Silvia PerettiMaurizio Federico
Mar 15, 2006·The Journal of Cell Biology·Amy M BoothStephen J Gould
Jan 16, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fangming XiuXuetao Cao
Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
Mar 26, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Shengming DaiGuisheng Li
Jan 16, 2009·Biochemical Society Transactions·Yoshiko UsamiHeinrich G Göttlinger
Jan 5, 2010·Advances in Experimental Medicine and Biology·Polly Roy, Rob Noad
Jul 6, 2010·Journal of Proteomics·Suresh MathivananRichard J Simpson
Dec 1, 2010·International Journal of Nanomedicine·Aaron TanAlexander M Seifalian
Dec 22, 2010·Seminars in Immunopathology·Nathalie Chaput, Clotilde Théry
Feb 22, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·John L FosterJ Victor Garcia
May 12, 2011·Cellular and Molecular Life Sciences : CMLS·Bence GyörgyEdit I Buzás
Oct 18, 2011·Vaccine·Zachary C HartmanHerbert K Lyerly
Jul 14, 2012·Nature Reviews. Immunology·Olivier P JoffreSebastian Amigorena
Oct 18, 2012·Cellular Microbiology·Sandra Columba Cabezas, Maurizio Federico

❮ Previous
Next ❯

Citations

Jul 2, 2020·Critical Reviews in Biotechnology·Javier Donoso-QuezadaJosé González-Valdez
Oct 1, 2019·International Journal of Cancer. Journal International Du Cancer·Javid Sadri NahandMichael R Hamblin
Jul 1, 2017·Frontiers in Pharmacology·Jiaqi WangPeng Cao
Dec 29, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Simona AnticoliMaurizio Federico
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Christos DogrammatzisMaria Kalamvoki
Jun 10, 2017·Biomarkers in Medicine·Sheng WangXiong-Wen Lv
Oct 27, 2018·Frontiers in Microbiology·Marcos V S DiasLuis L P daSilva
Jun 11, 2020·International Journal of Molecular Sciences·Linda HofmannMarie-Nicole Theodoraki
Feb 19, 2016·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Elena V Batrakova, Myung Soo Kim
May 28, 2020·Viruses·Flavia GiannessiElisabetta Affabris

❮ Previous
Next ❯