Single-cell mapping of combinatorial target antigens for CAR switches using logic gates

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Identification of optimal target antigens that distinguish cancer cells from normal surrounding tissue cells remains a key challenge in chimeric antigen receptor (CAR) cell therapy for tumors with intratumoral heterogeneity. In this study, we dissected tissue complexity to the level of individual cells through the construction of a single-cell expression atlas that integrates similar to 1.4 million tumor, tumor-infiltrating normal and reference normal cells from 412 tumors and 12 normal organs. We used a two-step screening method using random forest and convolutional neural networks to select gene pairs that contribute most to discrimination between individual malignant and normal cells. Tumor coverage and specificity are evaluated for the AND, OR and NOT logic gates based on the combinatorial expression pattern of the pairing genes across individual single cells. Single-cell transcriptome-coupled epitope profiling validates the AND, OR and NOT switch targets identified in ovarian cancer and colorectal cancer.
Publisher
NATURE PORTFOLIO
Issue Date
2023-11
Language
English
Article Type
Article
Citation

NATURE BIOTECHNOLOGY, v.41, no.11, pp.1593 - 1605

ISSN
1087-0156
DOI
10.1038/s41587-023-01686-y
URI
http://hdl.handle.net/10203/314759
Appears in Collection
MSE-Journal Papers(저널논문)BiS-Journal Papers(저널논문)
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