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Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
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3D tumor spheroid microarray for high-throughput, high-content natural killer cell-mediated cytotoxicity
Sneha Gopal1, Seok-Joon Kwon2, Bosung Ku3
1Department of Chemical and Biological Engineering, and Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Communications Biology
|July 22, 2021
Summary
A new 3D co-culture platform enables rapid screening of antibody-dependent cell-mediated cytotoxicity (ADCC) drug combinations for cancer immunotherapy. This tool aids in optimizing combination therapies and developing personalized treatments for solid tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Immunotherapy, particularly using natural killer (NK) cells and antibody-dependent cell-mediated cytotoxicity (ADCC), shows promise for treating solid tumors.
- Current methods lack tools for rapid screening and optimization of NK cell-based combination therapies in a 3D tumor microenvironment.
Purpose of the Study:
- To develop a high-throughput 3D co-culture platform for screening antibody-dependent cell-mediated cytotoxicity (ADCC) drug combinations.
- To evaluate the platform's ability to mimic tumor microenvironment conditions and assess combination therapy efficacy.
Main Methods:
- Development of a 330 micropillar-microwell sandwich platform for 3D co-culture of NK92-CD16 cells with pancreatic (MiaPaCa-2) and breast cancer cell lines (MCF-7, MDA-MB-231).
- Mimicking hypoxic tumor microenvironment conditions.
- Testing NK-cell mediated cytotoxicity in combination with Trastuzumab and Atezolizumab.
Main Results:
- The platform successfully supported 3D co-culture and mimicked tumor microenvironment hypoxia.
- Demonstrated NK-cell mediated cytotoxicity with Trastuzumab and Atezolizumab.
- Showed reduced EC50 values for paclitaxel in combination therapy, indicating enhanced efficacy.
Conclusions:
- The developed 3D platform facilitates rapid screening and optimization of ADCC-based immunotherapy combinations.
- This technology may accelerate the development of personalized cancer therapies using patient-derived cells.
