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

Author:

Valiullina Aigul Kh.1,Zmievskaya Ekaterina A.1,Ganeeva Irina A.1,Zhuravleva Margarita N.1,Garanina Ekaterina E.1,Rizvanov Albert A.1ORCID,Petukhov Alexey V.2,Bulatov Emil R.13ORCID

Affiliation:

1. Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia

2. Institute of Hematology, Almazov National Medical Research Center, 197341 Saint Petersburg, Russia

3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

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.

Funder

subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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