Melanoma protective antitumor immunity activated by catalytic DNA

Oncogene
Hong CaiLevon M Khachigian

Abstract

Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule inhibitors and immune checkpoint antibodies improve patient outcomes, most patients ultimately fail these therapies and alternative treatment strategies are urgently needed. DNAzymes have recently undergone clinical trials with signs of efficacy and no serious adverse events attributable to the DNAzyme. Here we investigated c-Jun expression in human primary and metastatic melanoma. We also explored the role of T cell immunity in DNAzyme inhibition of primary melanoma growth and the prevention of growth in non-treated tumors after the cessation of treatment in a mouse model. c-Jun was expressed in 80% of melanoma cells in human primary melanomas (n = 17) and in 83% of metastatic melanoma cells (n = 38). In contrast, c-Jun was expressed in only 11% of melanocytes in benign nevi (n = 24). Dz13, a DNAzyme targeting c-Jun/AP-1, suppressed both Dz13-injected and untreated B16F10 melanoma growth in the same mice, an abscopal effect relieved in each case by administration of anti-CD4/anti-CD8 antibodies. Dz13 increased levels of cleaved caspase-3 within the tumors. New, untreated melanomas grew poorly in mice previously treated with Dz13. Adm...Continue Reading

References

Apr 4, 1973·Nature: New Biology·I J Fidler
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S W Santoro, G F Joyce
Jun 13, 2001·Oncogene·E Shaulian, M Karin
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
May 6, 2004·Journal of the National Cancer Institute·Guishui ZhangLevon M Khachigian
Sep 24, 2004·Annals of Surgical Oncology·Miguel-Angel Perales, Jedd D Wolchok
Feb 24, 2005·Cancer Biology & Therapy·Zhaoyu Jin, Wafik S El-Deiry
Feb 1, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Edward L KornJohn M Kirkwood
Jan 13, 2012·Cancer Research·John C CastleUgur Sahin
Jun 23, 2012·Science Translational Medicine·Hong CaiLevon M Khachigian
Mar 26, 2013·Scientific Reports·Maya Kahan-HanumEhud Shapiro
Dec 10, 2013·European Journal of Cell Biology·Melanie KappelmannSilke Kuphal
Dec 11, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ya CaoLun-Quan Sun
May 2, 2014·Biochimica Et Biophysica Acta·Jingjing XieMing Wang
Feb 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maurizio Zanetti
May 20, 2015·The New England Journal of Medicine·Norbert KrugHarald Renz
Jul 17, 2015·JAMA Oncology·Douglas B Johnson, Jeffrey A Sosman
Sep 26, 2015·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Hojabr KakavandRichard A Scolyer
Dec 5, 2015·Frontiers in Immunology·Abhishek D GargPatrizia Agostinis
Feb 4, 2016·Immunology and Cell Biology·Elena ShklovskayaBarbara Fazekas de St. Groth
Mar 11, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jason MadoreJames S Wilmott
Jan 1, 2017·Microbial Pathogenesis·Zhaopei ZhangSanhu Wang
Apr 5, 2017·Nature Reviews. Clinical Oncology·Jason J LukeGeorgina V Long
May 19, 2017·Dermatology Practical & Conceptual·Zoe ApallaDemetrios Ioannides

❮ Previous
Next ❯

Citations

Jul 15, 2020·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Kelly A D F CastroAugusto C Tomé
Feb 15, 2019·Cancer Research·Levon M Khachigian
Jun 6, 2021·Journal of Inorganic Biochemistry·Francisco Rinaldi-NetoDenise Crispim Tavares

❮ Previous
Next ❯

Software Mentioned

ImageScope
Pro Plus
Image
Graphpad PRISM
DISCOVER

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.