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Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies

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Tumor Immunology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1393))

Abstract

Cellular immunotherapy targeting human tumor antigens is a promising strategy to treat solid tumors. Yet clinical results of cellular immunotherapy are disappointing. Moreover, the currently available in vitro human tumor models are not designed to study the optimization of T-cell therapies of solid tumors. Here, we describe a novel assay for multiparametric in situ analysis of therapeutic effects on individual human three-dimensional (3D) tumors. In this assay, tumors of several millimeter diameter are generated from human cancer cell lines of different tumor entities in a collagen type I microenvironment. A newly developed approach for efficient morphological analysis reveals that these in vitro tumors resemble many characteristics of the corresponding clinical cancers such as histological features, immunohistochemical staining patterns, distinct tumor growth compartments and heterogeneous protein expression. To assess the response to therapy with tumor antigen specific T-cells, standardized protocols are described to determine T-cell infiltration and tumor destruction by monitoring soluble factors and tumor growth. Human tumors engineered in 3D collagen scaffolds are excellent in vitro surrogates for avascular tumor stages allowing integrated analyses of the antitumor efficacy of cancer specific immunotherapy in situ.

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Author information

Authors and Affiliations

  1. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leident, The Netherlands

    Lothar Hambach, Andreas Buser, Nadine Pouw & Els Goulmy

  2. Department of Hematology, Hemostasis, Oncology and Stem cell transplantation Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Lothar Hambach

  3. Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland

    Andreas Buser

  4. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

    Marcel Vermeij & Theo van der Kwast

Authors
  1. Lothar Hambach
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  2. Andreas Buser
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  3. Marcel Vermeij
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  4. Nadine Pouw
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  5. Theo van der Kwast
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  6. Els Goulmy
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Corresponding author

Correspondence to Lothar Hambach .

Editor information

Editors and Affiliations

  1. Division of Regenerative Medicine, S. Raffaele Scientific Institute, Milano, Italy

    Attilio Bondanza

  2. Stem Cells and Gene Therapy, S. Raffaele Scientific Institute Division of Regenerative Medicine, Milano, Italy

    Monica Casucci

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© 2016 Springer Science+Business Media New York

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Hambach, L., Buser, A., Vermeij, M., Pouw, N., van der Kwast, T., Goulmy, E. (2016). Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies. In: Bondanza, A., Casucci, M. (eds) Tumor Immunology. Methods in Molecular Biology, vol 1393. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3338-9_15

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  • DOI: https://doi.org/10.1007/978-1-4939-3338-9_15

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3336-5

  • Online ISBN: 978-1-4939-3338-9

  • eBook Packages: Springer Protocols

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