Oncolytic Adenovirus Armed with BiTE, Cytokine, and Checkpoint Inhibitor Enables CAR T Cells to Control the Growth of Heterogeneous Tumors.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Caroline E PorterMasataka Suzuki

Abstract

No single cancer immunotherapy will likely defeat all evasion mechanisms of solid tumors, including plasticity of tumor antigen expression and active immune suppression by the tumor environment. In this study, we increase the breadth, potency, and duration of anti-tumor activity of chimeric antigen receptor (CAR) T cells using an oncolytic virus (OV) that produces cytokine, checkpoint blockade, and a bispecific tumor-targeted T cell engager (BiTE) molecule. First, we constructed a BiTE molecule specific for CD44 variant 6 (CD44v6), since CD44v6 is widely expressed on tumor but not normal tissue, and a CD44v6 antibody has been safely administered to cancer patients. We then incorporated this BiTE sequence into an oncolytic-helper binary adenovirus (CAdDuo) encoding an immunostimulatory cytokine (interleukin [IL]-12) and an immune checkpoint blocker (PD-L1Ab) to form CAdTrio. CD44v6 BiTE from CAdTrio enabled HER2-specific CAR T cells to kill multiple CD44v6+ cancer cell lines and to produce more rapid and sustained disease control of orthotopic HER2+ and HER2-/- CD44v6+ tumors than any component alone. Thus, the combination of CAdTrio with HER2.CAR T cells ensures dual targeting of two tumor antigens by engagement of distinct cla...Continue Reading

References

Dec 16, 1998·Japanese Journal of Cancer Research : Gann·T GotodaT Kakizoe
Dec 6, 2001·Gynecologic Oncology·A AyhanA Ayhan
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bernard M TijinkGuus A M S van Dongen
Nov 3, 2006·Cancer Research·Martin Götte, George W Yip
Jun 19, 2007·Cancer Research·Nabil AhmedStephen Gottschalk
Jul 9, 2011·Nature Immunology·E John Wherry
Aug 15, 2012·Human Gene Therapy·Kilian GuseBrendan Lee
Jan 16, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Masataka SuzukiBrendan Lee
Mar 25, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nabil AhmedStephen Gottschalk
Jun 11, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christine E BrownMichael C Jensen
Jun 4, 2016·Scientific Reports·Mireya Paulina VelasquezStephen Gottschalk
Feb 2, 2017·Cancer Research·Carlos Alberto FajardoRamon Alemany
Feb 10, 2017·Oncoimmunology·Norihiro WatanabeJuan F Vera
Oct 5, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amanda Rosewell ShawMasataka Suzuki
Oct 28, 2017·Nature Reviews. Cancer·Nicolas GengenbacherHellmut G Augustin
Feb 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·A J DavenportM R Jenkins
Jul 18, 2018·Cancer Discovery·Clare Y SlaneyMichael H Kershaw
Aug 24, 2018·Cancer Discovery·Robbie G Majzner, Crystal L Mackall
Jan 23, 2019·Molecular Therapy. Methods & Clinical Development·Sonia GuedanMarcela V Maus
Jul 12, 2019·Nature Reviews. Drug Discovery·Kevin HarringtonJean-Charles Soria
Aug 14, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stacey L DoranChristian S Hinrichs
Jan 1, 2020·Molecular Therapy. Methods & Clinical Development·Amanda Rosewell Shaw, Masataka Suzuki

❮ Previous
Next ❯

Citations

Jun 13, 2020·Cancers·Praveensingh B HajeriMasato Yamamoto
Jul 1, 2020·Journal of Hematology & Oncology·Otto HemminkiAkseli Hemminki
Feb 6, 2021·Cancer Immunology, Immunotherapy : CII·Jianhan HuangLiangxue Zhou
Dec 3, 2020·Cancers·Bharat BurmanDmitriy Zamarin
Jan 21, 2021·Cancers·Jim MiddelburgThorbald van Hall
Nov 19, 2020·Cancers·Malin Peter, Florian Kühnel
Oct 31, 2020·Journal for Immunotherapy of Cancer·Jennifer L GardellCourtney A Crane
Feb 12, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mary K McKennaMalcolm K Brenner
Dec 23, 2020·Human Gene Therapy·Kyle McGrath, Gianpietro Dotti
Feb 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Katarzyna C PituchIrina V Balyasnikova
Mar 6, 2021·Molecular Therapy. Methods & Clinical Development·Dominik BrücherAndreas Plückthun
Mar 21, 2021·Communications Biology·Amanda Rosewell ShawMasataka Suzuki
Mar 26, 2021·Molecular Cancer·Tina BriolayNicolas Boisgerault
Apr 4, 2021·Cancers·Laura Evgin, Richard G Vile
Apr 18, 2021·Journal of Hematology & Oncology·Johannes P W Heidbuechel, Christine E Engeland
Apr 19, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·John C Bell
May 28, 2021·Biomarker Research·Shujie ZhouJinming Yu
Jun 8, 2021·Frontiers in Immunology·Lele MiaoYumin Li
Jun 24, 2021·Cancer Gene Therapy·Ramazan RezaeiAkbar Ghorbani Alvanegh
Aug 10, 2021·Frontiers in Microbiology·Yaqi ZhaoBin Xu
Aug 28, 2021·International Journal of Molecular Sciences·Cole W D Peters, Fares Nigim
Sep 27, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jessica WagnerStephen Gottschalk

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.