Radiation and PD-(L)1 treatment combinations: immune response and dose optimization via a predictive systems model

Journal for Immunotherapy of Cancer
Yuri KosinskyGabriel Helmlinger

Abstract

Numerous oncology combination therapies involving modulators of the cancer immune cycle are being developed, yet quantitative simulation models predictive of outcome are lacking. We here present a model-based analysis of tumor size dynamics and immune markers, which integrates experimental data from multiple studies and provides a validated simulation framework predictive of biomarkers and anti-tumor response rates, for untested dosing sequences and schedules of combined radiation (RT) and anti PD-(L)1 therapies. A quantitative systems pharmacology model, which includes key elements of the cancer immunity cycle and the tumor microenvironment, tumor growth, as well as dose-exposure-target modulation features, was developed to reproduce experimental data of CT26 tumor size dynamics upon administration of RT and/or a pharmacological IO treatment such as an anti-PD-L1 agent. Variability in individual tumor size dynamics was taken into account using a mixed-effects model at the level of tumor-infiltrating T cell influx. The model allowed for a detailed quantitative understanding of the synergistic kinetic effects underlying immune cell interactions as linked to tumor size modulation, under these treatments. The model showed that the...Continue Reading

References

Dec 9, 1976·Nature·L NortonA E Bogden
Jan 1, 1985·International Journal of Radiation Oncology, Biology, Physics·M V WilliamsJ F Fowler
Jan 23, 2004·Nature Reviews. Cancer·Annapoorni Rangarajan, Robert A Weinberg
Feb 3, 2007·Journal of Theoretical Biology·Peter S KimDoron Levy
Aug 30, 2008·Seminars in Radiation Oncology·John P KirkpatrickLawrence B Marks
Apr 30, 2009·Nucleic Acids Research·Aroumougame Asaithamby, David J Chen
Jul 4, 2009·The Lancet Oncology·Silvia C Formenti, Sandra Demaria
Jul 28, 2010·The Journal of Experimental Medicine·Elizabeth D ThompsonVictor H Engelhard
Jul 21, 2011·British Journal of Cancer·K J HarringtonT Illidge
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jun 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anurag GuptaMaries van den Broek
May 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hua LiangYang-Xin Fu
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Nov 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kathleen M KokolusElizabeth A Repasky
Jan 3, 2014·The Journal of Clinical Investigation·Liufu DengYang-Xin Fu
Dec 8, 2014·Seminars in Radiation Oncology·Encouse B Golden, Lionel Apetoh
Dec 17, 2014·Frontiers in Oncology·Ralph E VatnerSilvia C Formenti
Feb 27, 2015·Cancer Immunology Research·Stephen L ShiaoLisa M Coussens
Apr 15, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander FilatenkovSamuel Strober
Jun 25, 2015·Nature Reviews. Cancer·Holly E BarkerKevin J Harrington
Aug 14, 2015·JAMA Oncology·Sandra DemariaSilvia C Formenti
Nov 26, 2015·Nature Reviews. Cancer·Philipp M AltrockFranziska Michor
Nov 26, 2015·Nature Reviews. Clinical Oncology·Dominique BarbolosiNicolas André
Dec 30, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K A AhmedG T Gibney
Feb 28, 2016·Theoretical Biology & Medical Modelling·Yoichi WatanabeSusanta K Hui
Apr 16, 2016·Nature Reviews. Cancer·Suzanne L TopalianDrew M Pardoll
Jun 2, 2016·Nature Reviews. Clinical Oncology·Ricky A SharmaUNKNOWN NCRI CTRad Academia-Pharma Joint Working Group
Jun 16, 2016·Cancer Research·Raphael SerreDominique Barbolosi
Sep 24, 2016·Journal for Immunotherapy of Cancer·Josephine KangSilvia Formenti
Nov 3, 2016·The New England Journal of Medicine·Vassiliki A Boussiotis
Dec 8, 2016·Cancer Immunology Research·Suzanne I S MoselyRobert W Wilkinson
Jan 7, 2017·Nature Reviews. Drug Discovery·W Joost LesterhuisRichard A Lake
Jan 18, 2017·Nature Reviews. Clinical Oncology·Ralph R WeichselbaumYang-Xin Fu
May 24, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Simon J DovediTimothy M Illidge
Jul 1, 2017·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Luke R G PikeJonathan D Schoenfeld

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Citations

Dec 19, 2018·Physics in Medicine and Biology·Damijan ValentinuzziRobert Jeraj
Mar 27, 2019·Clinical Pharmacology and Therapeutics·Jin NiuDonald E Mager
Apr 26, 2019·Radiation Research·Cameron R MacDonaldElizabeth A Repasky
Jan 19, 2020·Cancer Immunology, Immunotherapy : CII·Michael HaderUdo S Gaipl
Jun 23, 2020·Clinical Pharmacology and Therapeutics·James W T YatesPaolo Vicini
Jun 20, 2020·Clinical Pharmacology and Therapeutics·Sebastien Benzekry
Jul 21, 2020·Clinical Pharmacology and Therapeutics·Vijayalakshmi ChelliahAndrzej M Kierzek
Feb 13, 2019·Frontiers in Immunology·Evgeni V NikolaevEduardo D Sontag
Sep 20, 2019·CPT: Pharmacometrics & Systems Pharmacology·Erica L BradshawJason R Chan
Jun 27, 2019·The AAPS Journal·Mohammad JafarnejadAleksander S Popel
Jun 28, 2019·Nature Reviews. Clinical Oncology·Clemens GrassbergerJay S Loeffler
Oct 5, 2019·Human Vaccines & Immunotherapeutics·J Milburn JessupAbid R Mattoo
Oct 23, 2020·Physics in Medicine and Biology·Damijan Valentinuzzi, Robert Jeraj
Nov 19, 2020·Journal of Clinical Pharmacology·Anwesha ChaudhuryAndrew M Stein
Apr 3, 2021·Frontiers in Oncology·Thomas FriedrichMarco Durante
Aug 1, 2019·The Lancet Oncology·Eric DeutschGuido Kroemer
May 5, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yixin TanMei Yi
Jul 10, 2021·Chaos·Jacques BélairJohn G Milton
Aug 27, 2021·Immunotherapy·Joseph D Butner, Zhihui Wang
Oct 9, 2021·Journal of Pharmacokinetics and Pharmacodynamics·Tim CardilinJohan Gabrielsson

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Software Mentioned

Monolix®
IQM systems pharmacology and pharmacometrics toolbox
MATLAB®
R
plot3D
ggplot2

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