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.
“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]
The Introduction and Discussion discuss immunotherapy potency assays during development and manufacturing, but neither describes EU clinical trial phases or compares European GMP requirements with those elsewhere. Searches for the EU trial-phase structure and stricter GMP regulations found no passage addressing either claim. (LLM, conf=0.74)
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- 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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