Combination treatment with hypofractionated radiotherapy plus IL-2/anti-IL-2 complexes and its theranostic evaluation

Journal for Immunotherapy of Cancer
Hua JingGabriele Niedermann

Abstract

Immunogenic radiotherapy (RT) can act synergistically with immune checkpoint blockers (ICBs). However, alternatives are needed for non-responding patients and those with pre-existing or ICB-induced autoimmune symptoms. Combination of RT with IL-2 could be an alternative. But IL-2 has a short half-life, and, by binding to its high-affinity receptor, it strongly stimulates immunosuppressive CD4+ Tregs and seems to promote potentially life-threatening vascular leakage. IL-2/anti-IL-2 complexes (IL-2c), which bind to the low-affinity receptor, have been reported to circumvent these disadvantages but they have not yet been thoroughly tested in conjunction with radiotherapy. We evaluated, in three mouse models, the antitumoral effects induced by hypofractionated RT (hRT) plus IL-2c. We also used non-invasive imaging with a newly developed PET tracer based on therapeutically active IL-2c and a PD-L1 PET tracer for the theranostic evaluation of the treatment and its side effects. Treatment of mice bearing established B16 melanomas with hRT + IL-2c was superior to hRT + uncomplexed IL-2 or hRT alone; IL-2c alone was not effective. hRT + IL-2c was also synergistic in mice bearing C51 colon carcinomas or 4T1 mammary carcinomas. The better...Continue Reading

References

Nov 1, 1992·Journal of Immunotherapy·J R LangeS A Rosenberg
Mar 4, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·H MaedaK Hori
Dec 3, 2003·Molecular Imaging·Andreas Markus Loening, Sanjiv Sam Gambhir
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amit A LugadeEdith M Lord
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daisuke KamimuraMasaaki Murakami
Aug 1, 2007·The Journal of Experimental Medicine·Daisuke Kamimura, Michael J Bevan
Oct 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jakub TomalaMarek Kovar
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sven LétourneauOnur Boyman
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Carsten KriegOnur Boyman
Jul 9, 2011·Nature Immunology·E John Wherry
Feb 22, 2012·Nature Reviews. Immunology·Onur Boyman, Jonathan Sprent
Apr 14, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Valentina Di GialleonardoErik F J De Vries
Jun 8, 2012·Science Translational Medicine·Steven K SeungWalter J Urba
Jul 12, 2013·Theranostics·Chenxi WuXiaoyuan Chen
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Simone GaedickeGabriele Niedermann
Jun 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Steven A Rosenberg
Oct 2, 2014·Current Opinion in Chemical Biology·Rodney A RosaliaOnur Boyman
Jan 2, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Catharina M L ZegersPhilippe Lambin
Mar 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Alice TzengK Dane Wittrup
Aug 14, 2015·JAMA Oncology·Sandra DemariaSilvia C Formenti
Nov 18, 2015·Trends in Immunology·Natalia Arenas-RamirezOnur Boyman
Jan 15, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J M MichotO Lambotte
Apr 10, 2016·Current Opinion in Immunology·Dario Neri, Paul M Sondel
Jul 23, 2016·Theranostics·Michael HettichGabriele Niedermann
Nov 1, 2016·Nature Reviews. Immunology·Lorenzo GalluzziGuido Kroemer
Dec 3, 2016·Science Translational Medicine·Natalia Arenas-RamirezOnur Boyman
Dec 27, 2016·Science Immunology·Michael SpiottoRalph R Weichselbaum
Jan 24, 2017·Cell·Matthew H SpitzerEdgar G Engleman
May 6, 2017·The Journal of Experimental Medicine·Byron H KwanK Dane Wittrup
May 27, 2017·Advanced Drug Delivery Reviews·Lauren MillingDarrell J Irvine

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Citations

Sep 12, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ren LuoGabriele Niedermann
Dec 24, 2020·Nature Communications·Dilara SahinOnur Boyman

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Methods Mentioned

BETA
transgenic
xenografts
flow cytometry
size exclusion chromatography
FACS
Size
Flow

Software Mentioned

GraphPad
FACSuite
GraphPad Prism
AMIDE

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