Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity
CAR-T therapy has revolutionized the field of oncology, offering a promising treatment option for cancer patients. However, the significant morbidity associated with therapy-related toxicity presents a major challenge to its widespread use. Despite extensive research into the underlying mechanisms o...
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MDPI AG
2024-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/22/1892 |
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| author | Aigul R. Rakhmatullina Mariya A. Zolotykh Yuliya V. Filina Aigul Kh. Valiullina Ekaterina A. Zmievskaya Dina U. Gafurbaeva Aisylu R. Sagdeeva Emil R. Bulatov Albert A. Rizvanov Regina R. Miftakhova |
| author_facet | Aigul R. Rakhmatullina Mariya A. Zolotykh Yuliya V. Filina Aigul Kh. Valiullina Ekaterina A. Zmievskaya Dina U. Gafurbaeva Aisylu R. Sagdeeva Emil R. Bulatov Albert A. Rizvanov Regina R. Miftakhova |
| author_sort | Aigul R. Rakhmatullina |
| collection | DOAJ |
| description | CAR-T therapy has revolutionized the field of oncology, offering a promising treatment option for cancer patients. However, the significant morbidity associated with therapy-related toxicity presents a major challenge to its widespread use. Despite extensive research into the underlying mechanisms of CAR-T therapy-related toxicity, there are still many unknowns. Furthermore, the lack of adequate in vitro models for assessing immunotoxicity and neurotoxicity further complicates the development of safer cellular therapies. Previously in our laboratory, we developed cancer-stroma spheres (CSS) composed of prostate adenocarcinoma PC3 cells and mesenchymal stem cells (MSC). Herein we present evidence that multicellular CSS could serve as a valuable in vitro model for toxicity studies related to CAR-T therapy. CSS containing CD19-overexpressing PC3M cells exhibited increased secretion of CAR-T cell toxicity-associated IL-8, MCP-1, and IP-10 in the presence of anti-CD19 CAR-T cells, compared to spheres derived from single cell types. |
| format | Article |
| id | doaj-art-bbbfc8938c3641e7bc78e8dd68b1a25d |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-bbbfc8938c3641e7bc78e8dd68b1a25d2025-08-20T02:28:08ZengMDPI AGCells2073-44092024-11-011322189210.3390/cells13221892Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated ToxicityAigul R. Rakhmatullina0Mariya A. Zolotykh1Yuliya V. Filina2Aigul Kh. Valiullina3Ekaterina A. Zmievskaya4Dina U. Gafurbaeva5Aisylu R. Sagdeeva6Emil R. Bulatov7Albert A. Rizvanov8Regina R. Miftakhova9Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaCAR-T therapy has revolutionized the field of oncology, offering a promising treatment option for cancer patients. However, the significant morbidity associated with therapy-related toxicity presents a major challenge to its widespread use. Despite extensive research into the underlying mechanisms of CAR-T therapy-related toxicity, there are still many unknowns. Furthermore, the lack of adequate in vitro models for assessing immunotoxicity and neurotoxicity further complicates the development of safer cellular therapies. Previously in our laboratory, we developed cancer-stroma spheres (CSS) composed of prostate adenocarcinoma PC3 cells and mesenchymal stem cells (MSC). Herein we present evidence that multicellular CSS could serve as a valuable in vitro model for toxicity studies related to CAR-T therapy. CSS containing CD19-overexpressing PC3M cells exhibited increased secretion of CAR-T cell toxicity-associated IL-8, MCP-1, and IP-10 in the presence of anti-CD19 CAR-T cells, compared to spheres derived from single cell types.https://www.mdpi.com/2073-4409/13/22/1892CAR-T therapycytokine release syndromeimmune effector cell-associated neurotoxicity syndromecancer-stroma spheresmesenchymal stem cellIL-8 |
| spellingShingle | Aigul R. Rakhmatullina Mariya A. Zolotykh Yuliya V. Filina Aigul Kh. Valiullina Ekaterina A. Zmievskaya Dina U. Gafurbaeva Aisylu R. Sagdeeva Emil R. Bulatov Albert A. Rizvanov Regina R. Miftakhova Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity Cells CAR-T therapy cytokine release syndrome immune effector cell-associated neurotoxicity syndrome cancer-stroma spheres mesenchymal stem cell IL-8 |
| title | Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity |
| title_full | Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity |
| title_fullStr | Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity |
| title_full_unstemmed | Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity |
| title_short | Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity |
| title_sort | multicellular cancer stroma spheres css for in vitro assessment of car t cell associated toxicity |
| topic | CAR-T therapy cytokine release syndrome immune effector cell-associated neurotoxicity syndrome cancer-stroma spheres mesenchymal stem cell IL-8 |
| url | https://www.mdpi.com/2073-4409/13/22/1892 |
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