Evaluation of CAR-T Cells' Cytotoxicity against Modified Solid Tumor Cell Lines

评估CAR-T细胞对改良实体瘤细胞系的细胞毒性

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作者:Aigul Kh Valiullina, Ekaterina A Zmievskaya, Irina A Ganeeva, Margarita N Zhuravleva, Ekaterina E Garanina, Albert A Rizvanov, Alexey V Petukhov, Emil R Bulatov

Abstract

In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines-lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells' monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome.

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