A computational diffusion model to study antibody transport within reconstructed tumor microenvironments

BMC Bioinformatics
Ana Luísa CartaxoInês A Isidro

Abstract

Antibodies revolutionized cancer treatment over the past decades. Despite their successfully application, there are still challenges to overcome to improve efficacy, such as the heterogeneous distribution of antibodies within tumors. Tumor microenvironment features, such as the distribution of tumor and other cell types and the composition of the extracellular matrix may work together to hinder antibodies from reaching the target tumor cells. To understand these interactions, we propose a framework combining in vitro and in silico models. We took advantage of in vitro cancer models previously developed by our group, consisting of tumor cells and fibroblasts co-cultured in 3D within alginate capsules, for reconstruction of tumor microenvironment features. In this work, an experimental-computational framework of antibody transport within alginate capsules was established, assuming a purely diffusive transport, combined with an exponential saturation effect that mimics the saturation of binding sites on the cell surface. Our tumor microenvironment in vitro models were challenged with a fluorescent antibody and its transport recorded using light sheet fluorescence microscopy. Diffusion and saturation parameters of the computational...Continue Reading

References

Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·D A BerkR K Jain
May 8, 2001·Annals of Biomedical Engineering·M PraxmarerW W van Osdol
Jan 28, 2003·Annals of Botany·Xinyou YinHuub J Spiertz
Apr 11, 2003·European Journal of Histochemistry : EJH·M A CroceI Pasquali-Ronchetti
May 4, 2004·Microvascular Research·Edward B BrownRakesh K Jain
Apr 1, 2005·Theoretical Biology & Medical Modelling·Mohammad TabatabaiZoran Bursac
Jul 25, 2006·Nature Reviews. Cancer·Andrew I Minchinton, Ian F Tannock
Nov 4, 2011·Trends in Cell Biology·Robert S FischerClare M Waterman
Apr 28, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tracy A Denison, You Han Bae
May 30, 2013·Frontiers in Oncology·Katarzyna A RejniakDavid L Morse
Mar 14, 2014·Journal of the Royal Society, Interface·C M GrohR M Phillips
May 16, 2014·Clinical Pharmacology and Therapeutics·I Fuso NeriniM D'Incalci
Nov 26, 2015·Biomedical Optics Express·Emilio J GualdaNuno Moreno
Sep 25, 2016·Proceedings of the National Academy of Sciences of the United States of America·Weijing HanLiyu Liu
Nov 11, 2017·Nature Reviews. Cancer·Mark W Dewhirst, Timothy W Secomb
Jan 10, 2018·Frontiers in Immunology·Isabel Corraliza-GorjónLeonor Kremer
Feb 10, 2018·Bulletin of Mathematical Biology·Aleksandra Karolak, Katarzyna A Rejniak
Feb 25, 2018·Biomaterials·Sofia P RebeloCatarina Brito
Apr 3, 2018·Trends in Cancer·Sara NizzeroMauro Ferrari
Apr 14, 2018·Nature Communications·Daniel RosenblumDan Peer
Mar 8, 2019·Journal of Experimental & Clinical Cancer Research : CR·Neel I NissenNicholas Willumsen

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Methods Mentioned

BETA
fluorescence microscopy
PCR
chip

Software Mentioned

Image J
ImageJ
Python
Python Imaging Library ( PIL )
LSFM
SPIM
fluid
LabVIEW

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