Systematic Characterization of AML Cell Lines to Support Preclinical In Vitro CAR-T Research
- 1Center for Precision Genetic Technologies for Medicine, National Medical Research Center for Hematology, Moscow 125167, Russia
- 2National Medical Research Center for Hematology, Moscow 125167, Russia
Abstract
The development of chimeric antigen receptor (CAR) T cell therapies for acute myeloid leukemia (AML) remains challenging, underscoring the need for reliable preclinical models. Although AML cell lines are widely used in CAR-T studies, their ability to reflect clinically relevant antigen expression patterns and functional characteristics of primary AML cells has not been systematically evaluated. We characterized nine AML cell lines (KG-1, HL-60, Kasumi-1, OCI-AML2, OCI-AML5, THP-1, U-937, MV4-11, and MOLM-13) as targets for in vitro CAR-T studies. We assessed the expression of established CAR-T target antigens (e.g., CLL1, CD33), cell lines similarity to minimal residual disease (MRD) cells and matched healthy monocytes from 161 AML patients, the expression of emerging AML-associated antigens (Siglec-6, CSF1R, and CD70), growth behavior, and susceptibility to non-specific killing by non-transduced T cells. AML cell lines demonstrated substantial heterogeneity in antigen expression with several cell lines showing antigen densities exceeding those observed in AML blasts. Several widely used lines, including U-937, were susceptible to non-transduced T-cell cytotoxicity, potentially confounding CAR-T functional assays and overestimating CAR-T activity in vitro. The examined parameters were integrated into a scoring framework to rank AML cell lines according to their suitability for in vitro CAR-T studies. Based on this framework and additional assay-related considerations, OCI-AML2, OCI-AML5, MV4-11, and MOLM-13 were identified as most suitable for in vitro evaluation of CAR-T products, particularly those targeting CD33 and CLL1. These findings may facilitate more informed selection of AML cell lines for preclinical development of CAR-T therapies for AML.
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BibTeX
@article{davydova2026systematic,
title = {{Systematic Characterization of AML Cell Lines to Support Preclinical In Vitro CAR-T Research}},
author = {Vassa D. Davydova and Anastasia A. Zotova and Nikolay M. Kapranov and Dmitry V. Dianov and Yulia O. Davydova and Tatiana A. Nenasheva and Irina Y. Zaichenko and Sergei D. Losev and Kseniia A. Nikiforova and Irina V. Galtseva and Apollinariya V. Bogolyubova},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211964},
url = {https://www.mdpi.com/2073-4409/15/21/1964},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Systematic Characterization of AML Cell Lines to Support Preclinical In Vitro CAR-T Research
AU - Vassa D. Davydova
AU - Anastasia A. Zotova
AU - Nikolay M. Kapranov
AU - Dmitry V. Dianov
AU - Yulia O. Davydova
AU - Tatiana A. Nenasheva
AU - Irina Y. Zaichenko
AU - Sergei D. Losev
AU - Kseniia A. Nikiforova
AU - Irina V. Galtseva
AU - Apollinariya V. Bogolyubova
PY - 2026
DA - 2026/10/28
JO - Cells
DO - 10.3390/cells15211964
UR - https://www.mdpi.com/2073-4409/15/21/1964
AB - The development of chimeric antigen receptor (CAR) T cell therapies for acute myeloid leukemia (AML) remains challenging, underscoring the need for reliable preclinical models. Although AML cell lines are widely used in CAR-T studies, their ability to reflect clinically relevant antigen expression patterns and functional characteristics of primary AML cells has not been systematically evaluated. We characterized nine AML cell lines (KG-1, HL-60, Kasumi-1, OCI-AML2, OCI-AML5, THP-1, U-937, MV4-11, and MOLM-13) as targets for in vitro CAR-T studies. We assessed the expression of established CAR-T target antigens (e.g., CLL1, CD33), cell lines similarity to minimal residual disease (MRD) cells and matched healthy monocytes from 161 AML patients, the expression of emerging AML-associated antigens (Siglec-6, CSF1R, and CD70), growth behavior, and susceptibility to non-specific killing by non-transduced T cells. AML cell lines demonstrated substantial heterogeneity in antigen expression with several cell lines showing antigen densities exceeding those observed in AML blasts. Several widely used lines, including U-937, were susceptible to non-transduced T-cell cytotoxicity, potentially confounding CAR-T functional assays and overestimating CAR-T activity in vitro. The examined parameters were integrated into a scoring framework to rank AML cell lines according to their suitability for in vitro CAR-T studies. Based on this framework and additional assay-related considerations, OCI-AML2, OCI-AML5, MV4-11, and MOLM-13 were identified as most suitable for in vitro evaluation of CAR-T products, particularly those targeting CD33 and CLL1. These findings may facilitate more informed selection of AML cell lines for preclinical development of CAR-T therapies for AML.
SN - 2073-4409
ER -