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

深度学习揭示全身癌症转移和治疗性抗体靶向

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作者:Chenchen Pan, Oliver Schoppe, Arnaldo Parra-Damas, Ruiyao Cai, Mihail Ivilinov Todorov, Gabor Gondi, Bettina von Neubeck, Nuray Böğürcü-Seidel, Sascha Seidel, Katia Sleiman, Christian Veltkamp, Benjamin Förstera, Hongcheng Mai, Zhouyi Rong, Omelyan Trompak, Alireza Ghasemigharagoz, Madita Alice Reim

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.

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