The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
In vitro immunotherapy potency assays using real-time cell analysis
Open accessAbstract
A growing understanding of the molecular interactions between immune effector cells and target tumor cells, coupled with refined gene therapy approaches, are giving rise to novel cancer immunotherapeutics with remarkable efficacy in the clinic against both solid and liquid tumors. While immunotherapy holds tremendous promise for treatment of certain cancers, significant challenges remain in the clinical translation to many other types of cancers and also in minimizing adverse effects. Therefore, there is an urgent need for functional potency assays, in vitro and in vivo, that could model the complex interaction of immune cells with tumor cells and can be used to rapidly test the efficacy of different immunotherapy approaches, whether it is small molecule, biologics, cell therapies or combinations thereof. Herein we report the development of an xCELLigence real-time cytolytic in vitro potency assay that uses cellular impedance to continuously monitor the viability of target tumor cells while they are being subjected to different types of treatments. Specialized microtiter plates containing integrated gold microelectrodes enable the number, size, and surface attachment strength of adherent target tumor cells to be selectively monitored within a heterogeneous mixture that includes effector cells, antibodies, small molecules, etc. Through surface-tethering approach, the killing of liquid cancers can also be monitored. Using NK92 effector cells as example, results from RTCA potency assay are very well correlated with end point data from image-based assays as well as flow cytometry. Several effector cells, i.e., PBMC, NK, CAR-T were tested and validated as well as biological molecules such as Bi-specific T cell Engagers (BiTEs) targeting the EpCAM protein expressed on tumor cells and blocking antibodies against the immune checkpoint inhibitor PD-1. Using the specifically designed xCELLigence immunotherapy software, quantitative parameters such as KT50 (the amount of time it takes to kill 50% of the target tumor cells) and % cytolysis are calculated and used for comparing the relative efficacy of different reagents. In summary, our results demonstrate the xCELLigence platform to be well suited for potency assays, providing quantitative assessment with high reproducibility and a greatly simplified work flow.
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“A similar clinical trial phase structure exists in the European Union, although some GMP regulations are stricter in Europe (132,133).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [132]
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Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Zhang, J.-H., Chung, T. D. Y., & Oldenburg, K. R. (1999) · SLAS Discovery · doi:10.1177/108705719900400206 · Cited by 6,847
Self-citationCancer immunotherapy: the beginning of the end of cancer?
Farkona, S., Diamandis, E. P., & Blasutig, I. M. (2016) · BMC Medicine · doi:10.1186/s12916-016-0623-5 · Cited by 1,231
Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway
Ohaegbulam, K. C., Assal, A., Lázár‐Molnár, E., Yao, Y., & Zang, X. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.10.009 · Cited by 861
Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape
Hegde, M. G., Mukherjee, M., Grada, Z., Pignata, A., Landi, D. B., Navai, S. A., Wakefield, A., Fousek, K., Bielamowicz, K., Chow, K. K. H., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83416 · Cited by 694
The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma
Mahoney, K. M., Freeman, G. J., & McDermott, D. F. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.02.018 · Cited by 589
The xCELLigence System for Real-Time and Label-Free Monitoring of Cell Viability
Ning, K., Wang, X., Xu, X., & Abassi, Y. A. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-108-6_6 · Cited by 441
Self-citationApplication of Real-Time Cell Electronic Sensing (RT-CES) Technology to Cell-Based Assays
Solly, K. J., Wang, X., Xu, X. Y., Strulovici, B., & Zheng, W. (2004) · Assay and Drug Development Technologies · doi:10.1089/adt.2004.2.363 · Cited by 383
Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens
Liu, X., Krawczyk, E., Suprynowicz, F. A., Palechor-Ceron, N., Yuan, H., Dakic, A., Simić, V., Zheng, Y., Sripadhan, P., Chen, C., et al. (2017) · Nature Protocols · doi:10.1038/nprot.2016.174 · Cited by 305
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Items 101–105 of 105
Plying potency assays for immunotherapy of solid tumors
Burns, J. S., Gjeta, R., Lesný, P., & Vives, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1770222
“As one of several notable examples (Table 2), the xCELLigence Real-Time Cell Analysis (RTCA) platform measures cellular impedance to non-invasively monitor surface-tethered tumor cell viability in the presence of immune effector cells without labels (186).”
A nanobody based approach to capture interactomes of dimeric protein complexes in living cells
Sleiman, N. H. (2024) · theses.fr (ABES) · doi:10.70675/633151e1z9a1cz42b0zbcbaz776177601937
xCELLigence™ RTCA system in cancer biology: innovations in real-time functional profiling
Andraos, C., Joseph, J. S., Utembe, W., Magogotya, M., Oriyomi, O. V., & Fagbohun, O. F. (2026) · Cytotechnology · doi:10.1007/s10616-026-01000-z
“The system relies on a gold microelectrode biosensor built into E-plate™ microtiter plates (Cerignoli et al. 2018).”
Impedance-Based Analysis of Functional Immunoassays Using Cultured Cells
Michaelis, S., Grimm, A.-K., Erl, J., Schmauss, J., Friedrich, S., Naber, T., Anczykowski, B., & Wegener, J. (2026) · Springer eBooks · doi:10.1007/978-3-662-71782-0_25
Chao, A., Lin, C.-Y., Tang, W.-J., Huang, C.-Y., Ren-Chin, W., Chao, A., & Lai, C. (2026) · Journal of Molecular Medicine · doi:10.1007/s00109-026-02732-3
“This label-free, impedance-based technology allows continuous monitoring of cell health, behavior, and function in real time [34 ].”
Metadata
- Authors
- Cerignoli, F., Abassi, Y. A., Lamarche, B. J., Guenther, G., Santa Ana, D., Guimet, D., Zhang, W., Zhang, J., & Xi, B.
- Affiliations
- ACEA Biosciences (United States) (US)
- Corresponding author
- Xi, Biao
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-03-02
- Volume
- 13
- Issue
- 3
- Pages
- e0193498
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5834184
- OpenAlex
- W2791857742
- Cited by
- 105
- References
- 47
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 6 · 2023: 13 · 2022: 15 · 2021: 19 · 2020: 11 · 2019: 17 · 2018: 2
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- cancer immunotherapy, potency assay, real-time cell monitoring, xCELLigence, tumor cell lysis, chimeric antigen receptor T cells, natural killer cells, bispecific T-cell engagers, EpCAM, gold microelectrodes, liquid tumors
- MeSH terms
- Epithelial Cell Adhesion Molecule, Antibodies, Biological Assay, Cytological Techniques, Humans, Immunotherapy, Leukocytes, Mononuclear, Apoptosis, Cell Line, Tumor, Programmed Cell Death 1 Receptor, MCF-7 Cells
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