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Ivana Kutle, Robert Polten, Jan Lennart Stalp, Jens Hachenberg, Felix Todzey, Ralf Hass, Katharina Zimmermann,
Juliane von der Ohe, Constantin von Kaisenberg, Lavinia Neubert, Jan C. Kamp, Dirk Schaudien, Ann-Kathrin Seyda,
Peter Hillemanns, Rüdiger Klapdor, Michael Alexander Morgan and Axel Schambach
Front. Immunol., Volume 15 - 2024 | https://doi.org/10.3389/fimmu.2024.1485461
Copyright © Authors 2024
This article is licensed under a Creative Commons Attribution 4.0 International License (CC BY).
Targeted therapies, particularly immune-based approaches like chimeric antigen receptor (CAR)-modified T cells, are becoming integral to cancer treatments. While CAR-based cell therapies have shown success, challenges remain with solid tumors, prompting exploration of alternative cell types and targets. Cervical cancer poses a serious health risk for women worldwide, and with limited treatment options for recurrent or metastatic cases, it presents an opportunity for the development of new therapies.. Mesothelin, highly expressed in cervical and other cancers but minimally in healthy tissues, is a promising target. Although anti-Mesothelin CAR-T cells have demonstrated efficacy in other cancers, their potential in cervical cancer remains largely unexplored.
Research AchievementsIn this study, cervical cancer cells 3D spheroids (Mesothelin+) were formed using PrimeSurfaceTM 96U plates. Anti-Mesothelin CAR-NK cells demonstrated high cytotoxicity against the cervical cancer cell spheroids, which corresponded to increased degranulation of CAR-NK cells upon exposure to Mesothelin+ target cells. Target antigen specificity of anti-Mesothelin CAR-NK cells was shown using CRISPR-Cas9-mediated knockout Mesothelin- cervical cancer cells in co culture experiments. Combination of anti-Mesothelin CAR-NK cells with chemotherapy revealed increased elimination of cancer cells as compared to monotherapy settings. These findings indicate the promise of anti-Mesothelin CAR-NK cells as a potential treatment option against cervical cancer, as well as other Mesothelin+ malignancies. |
![]() Efficient eradication of 3D tumor spheroids upon co-culture with anti-Mesothelin CAR-NK-92 cells |
Spheroid formation:
Cell: SiHa cell line,Cell density: 1000 cells/well
Meduim: complete RPMI medium
Seeding and culture condition: PrimeSurfaceTM 96U plates were centrifuged at 125 xg for 10 min and incubated for 3-5 days in a humidified incubator at 37°C with 5% CO2.
Spheroids were applied in 3D cytotoxicity assays: NK cells were added to the formed spheroids and co-culture for up tp 4 days
Cell viability was presented by fluorescent intensity
Cat # | Product name | Well | Color | Bottom design | Well Vol | Package |
---|---|---|---|---|---|---|
MS-9096UZ | PrimeSurface™ 96U | 96 | Transparent | U bottom | 300 μL | Individual packaging 20 plates per case |
Remark