Experimental cell research · 2019
In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Al-Samadi Ahmed, Poor Benedek, Tuomainen Katja, Liu Ville, Hyytiäinen Aini, Suleymanova Ilida, Mesimaki Karri, Wilkman Tommy, Mäkitie Antti, Saavalainen Päivi, Salo Tuula
Аннотация
OBJECTIVES: 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.
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.
Предметные рубрики MeSH
AgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkers, PharmacologicalCell Migration AssaysCell MovementCoculture TechniquesDrug Screening Assays, AntitumorEquipment DesignFemaleHead and Neck NeoplasmsHumansImmunologic FactorsImmunotherapyLab-On-A-Chip DevicesMaleMicrofluidicsMiddle AgedPrecancerous ConditionsPrecision MedicinePrimary Cell CulturePrognosisSquamous Cell Carcinoma of Head and NeckTissue ScaffoldsTumor Cells, Cultured