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3D tumor spheroid microarray for high-throughput, high-content natural killer cell-mediated cytotoxicity.

ABSTRACT: Immunotherapy has emerged as a promising approach to treating several forms of cancer. Use of immune cells, such as natural killer (NK) cells, along with small molecule drugs and antibodies through antibody dependent cell-mediated cytotoxicity (ADCC) has been investigated as a potential combination therapy for some difficult to treat solid tumors. Nevertheless, there remains a need to develop tools that support co-culture of target cancer cells and effector immune cells in a contextually relevant three-dimensional (3D) environment to provide a rapid means to screen for and optimize ADCC-drug combinations. To that end, here we have developed a high throughput 330 micropillar-microwell sandwich platform that enables 3D co-culture of NK92-CD16 cells with pancreatic (MiaPaCa-2) and breast cancer cell lines (MCF-7 and MDA-MB-231). The platform successfully mimicked hypoxic conditions found in a tumor microenvironment and was used to demonstrate NK-cell mediated cell cytotoxicity in combination with two monoclonal antibodies; Trastuzumab and Atezolizumab. The platform was also used to show dose response behavior of target cancer cells with reduced EC₅₀ values for paclitaxel (an anti-cancer chemotherapeutic) when treated with both NK cells and antibody. Such a platform may be used to develop more personalized cancer therapies using patient-derived cancer cells.

SUBMITTER: Gopal S

PROVIDER: S-EPMC8295284 | biostudies-literature |

REPOSITORIES: biostudies-literature

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3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay.

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| S-EPMC8744335 | biostudies-literature

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Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-02 | GSE175864 | GEO

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| S-EPMC7454010 | biostudies-literature

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