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In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients |
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| Author: | Al-Samadi, Ahmed1,2; Poor, Benedek2,3; Tuomainen, Katja1,2; |
| Organizations: |
1Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland 2Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland 3Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
4Department of Oral and Maxillofacial Surgery, HUS Helsinki University Hospital, Finland
5Department of Otorhinolaryngology - Head and Neck Surgery, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland 6Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 7Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Finland 8Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland 9Medical Research Centre, Oulu University Hospital, Oulu, Finland 10Helsinki University Hospital, Helsinki, Finland |
| Format: | article |
| Version: | accepted version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1.2 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2019120345390 |
| Language: | English |
| Published: |
Elsevier,
2019
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| Publish Date: | 2020-07-26 |
| Description: |
AbstractObjectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy. Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix “Myogel/fibrin” and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients′ serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated. Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent. Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients. see all
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| Series: |
Experimental cell research |
| ISSN: | 0014-4827 |
| ISSN-E: | 1090-2422 |
| ISSN-L: | 0014-4827 |
| Volume: | 383 |
| Issue: | 2 |
| Article number: | 111508 |
| DOI: | 10.1016/j.yexcr.2019.111508 |
| OADOI: | https://oadoi.org/10.1016/j.yexcr.2019.111508 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3122 Cancers |
| Subjects: | |
| Funding: |
We acknowledge the funders of this study: the Sigrid Jusélius Foundation, The Cancer Society of Finland, Oulu University Hospital MRC grant, the Emil Aaltonen Foundation, and Helsinki University Central Hospital Research Funds. |
| Copyright information: |
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |