High-throughput single-cell screening of a cross-lineage CAR library for early-stage CAR design and candidate discovery
- 1BOE Technology Group Co. Ltd., Beijing, China
- 2BOE Regenerative Medicine Technology Co. Ltd, Beijing, China
Abstract
Chimeric antigen receptor T cell therapy (CAR-T) has demonstrated promising efficacy in hematological malignancies, but translating that success to solid tumors remains challenging. Here, we construct a CAR library comprising approximately 1000 variants targeting prostate-specific membrane antigen by recombining transmembrane (TM), co-stimulatory, and activation domains from Natural Killer (NK) and T cell receptors. Single-cell screening identifies ICOSTM-containing variants with improved T cell activation; NK-derived activation domains, such as DAP10ζ, DAP12ζ, and FcRγζ, further augment the effector capacity. Gene regulatory network analysis reveals that CAR variants with elevated expression of T cell-activation-related transcription factors correlates with enhanced cell function. Overall, our study advances early-stage CAR design by expanding the repertoire of structural components from diverse immune cells, providing a scalable platform for identifying candidates with functional profiles comparable to clinical benchmarks.
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BibTeX
@article{jing2026highthroughput,
title = {{High-throughput single-cell screening of a cross-lineage CAR library for early-stage CAR design and candidate discovery}},
author = {Hairong Jing and Dan Yuan and Bangquan Ye and Jianlin Ma and Beiyuan Fan and Yunqing Mu and Yiquan Liu and Mingming Zhan and Shuai Liu and Zijian Zhao and Yanzhao Li and Zhiqiang Liu},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10514-3},
url = {https://doi.org/10.1038/s42003-026-10514-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - High-throughput single-cell screening of a cross-lineage CAR library for early-stage CAR design and candidate discovery
AU - Hairong Jing
AU - Dan Yuan
AU - Bangquan Ye
AU - Jianlin Ma
AU - Beiyuan Fan
AU - Yunqing Mu
AU - Yiquan Liu
AU - Mingming Zhan
AU - Shuai Liu
AU - Zijian Zhao
AU - Yanzhao Li
AU - Zhiqiang Liu
PY - 2026
DA - 2026/07/20
JO - Communications Biology
DO - 10.1038/s42003-026-10514-3
UR - https://doi.org/10.1038/s42003-026-10514-3
AB - Chimeric antigen receptor T cell therapy (CAR-T) has demonstrated promising efficacy in hematological malignancies, but translating that success to solid tumors remains challenging. Here, we construct a CAR library comprising approximately 1000 variants targeting prostate-specific membrane antigen by recombining transmembrane (TM), co-stimulatory, and activation domains from Natural Killer (NK) and T cell receptors. Single-cell screening identifies ICOSTM-containing variants with improved T cell activation; NK-derived activation domains, such as DAP10ζ, DAP12ζ, and FcRγζ, further augment the effector capacity. Gene regulatory network analysis reveals that CAR variants with elevated expression of T cell-activation-related transcription factors correlates with enhanced cell function. Overall, our study advances early-stage CAR design by expanding the repertoire of structural components from diverse immune cells, providing a scalable platform for identifying candidates with functional profiles comparable to clinical benchmarks.
SN - 2399-3642
ER -