Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 22, p 1892 (2024)
Druh dokumentu: article
ISSN: 13221892
2073-4409
DOI: 10.3390/cells13221892
Popis: 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.
Databáze: Directory of Open Access Journals
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