Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Journal: Cell
PMID: 31835038

Abstract

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.

Authors

  • Chenchen Pan
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Oliver Schoppe
    Department of Informatics, Technical University of Munich, 85748 Munich, Germany; Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
  • Arnaldo Parra-Damas
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Ruiyao Cai
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Mihail Ivilinov Todorov
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Graduate School of Systemic Neurosciences (GSN), 82152 Munich, Germany.
  • Gabor Gondi
    Research Unit Gene Vectors, Helmholtz Zentrum München, 81377 Munich, Germany.
  • Bettina von Neubeck
    Research Unit Gene Vectors, Helmholtz Zentrum München, 81377 Munich, Germany.
  • Nuray Böğürcü-Seidel
    Institute of Neuropathology, University of Giessen, 35390 Giessen, Germany.
  • Sascha Seidel
    Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60323 Frankfurt, Germany.
  • Katia Sleiman
    Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; Division of Translational Cancer Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
  • Christian Veltkamp
    Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; Division of Translational Cancer Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
  • Benjamin Förstera
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Hongcheng Mai
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Zhouyi Rong
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Omelyan Trompak
    Institute of Neuropathology, University of Giessen, 35390 Giessen, Germany.
  • Alireza Ghasemigharagoz
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Madita Alice Reimer
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Angel M Cuesta
    Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60323 Frankfurt, Germany.
  • Javier Coronel
    Department of Informatics, Technical University of Munich, 85748 Munich, Germany.
  • Irmela Jeremias
    Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Zentrum München, German Center for Environmental Health (HMGU), 81377 Munich, Germany; Department of Pediatrics, Dr. von Hauner Childrens Hospital, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; German Consortium for Translational Cancer Research (DKTK), Partnering Site Munich, 80336 Munich, Germany.
  • Dieter Saur
    Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; Division of Translational Cancer Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
  • Amparo Acker-Palmer
    Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60323 Frankfurt, Germany.
  • Till Acker
    Institute of Neuropathology, University of Giessen, 35390 Giessen, Germany.
  • Boyan K Garvalov
    Institute of Neuropathology, University of Giessen, 35390 Giessen, Germany; Department of Microvascular Biology and Pathobiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Bjoern Menze
  • Reinhard Zeidler
    Research Unit Gene Vectors, Helmholtz Zentrum München, 81377 Munich, Germany; Department for Otorhinolaryngology, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Ali Ertürk
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: erturk@helmholtz-muenchen.de.

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