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

Ana Luísa Cartaxo1,2, Jaime Almeida3,4, Emilio J Gualda5

  • 1iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.

BMC Bioinformatics
|November 18, 2020
PubMed
Summary

This study developed a computational and microscopy framework to track antibody transport in tumor microenvironment models. This tool helps understand how tumor components affect antibody delivery for improved cancer therapies.

Keywords:
3D in vitro cancer modelsAntibody diffusionComputational modellingLight sheet fluorescence microscopyTumor microenvironment

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Computational Biology

Background:

  • Antibody-based cancer therapies face challenges due to heterogeneous antibody distribution within tumors.
  • Tumor microenvironment (TME) components like cell types and extracellular matrix can impede antibody penetration.
  • Understanding these TME-antibody interactions is crucial for enhancing therapeutic efficacy.

Purpose of the Study:

  • To develop an integrated experimental-computational framework for simulating antibody transport within a reconstructed tumor microenvironment.
  • To investigate the influence of TME heterogeneity on antibody distribution and delivery to cancer cells.

Main Methods:

  • Established 3D in vitro cancer models using co-cultured tumor cells and fibroblasts in alginate capsules.
  • Developed a computational model simulating antibody transport via diffusion and cell-binding saturation.
  • Utilized light-sheet fluorescence microscopy to experimentally validate the computational model's predictions.

Main Results:

  • An experimental-computational framework accurately simulated antibody distribution within the TME models (RMSE < 5%).
  • The framework successfully modeled antibody transport, incorporating diffusion and saturation effects.
  • The computational model can simulate various TME element distributions, mimicking experimental observations.

Conclusions:

  • A novel computational and microscopy framework was established to track and simulate antibody transport in the TME.
  • This framework complements existing in vitro models and offers a valuable tool for studying TME influences on antibody delivery.
  • The developed tool has the potential to guide the optimization of antibody-based cancer treatments.