The lack of tumor-specific surface antigens has limited the application of CAR T cells in solid tumors. A new AND-gated CAR T cell system repurposes proximal T cell signaling proteins to restrict activation to dual antigen encounter, mitigating on-target, off-tumor toxicity while preserving antitumor efficacy in preclinical models.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Advancing cancer gene therapy: the emerging role of nanoparticle delivery systems
Journal of Nanobiotechnology Open Access 20 May 2025
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout

References
Tousley, A. M. et al. Nature 615, 507–516 (2023).
June, C. H. & Sadelain, M. N. Engl. J. Med. 379, 64–73 (2018).
Kloss, C. C., Condomines, M., Cartellieri, M., Bachmann, M. & Sadelain, M. Nat. Biotechnol. 31, 71–75 (2013).
Roybal, K. T. et al. Cell 167, 419–432 e416 (2016).
Cho, J. H., Collins, J. J. & Wong, W. W. Cell 173, 1426–1438 e1411 (2018).
Lajoie, M. J. et al. Science 369, 1637–1643 (2020).
Srivastava, S. et al. Cancer Cell 35, 489–503 e488 (2019).
Majzner, R. G. et al. Cancer Discov. 10, 702–723 (2020).
Hamieh, M. et al. Nature 568, 112–116 (2019).
Zhao, Z. et al. Cancer Cell 28, 415–428 (2015).
Daniels, K. G. et al. Science 378, 1194–1200 (2022).
Kawalekar, O. U. et al. Immunity 44, 380–390 (2016).
Mackensen, A. et al. Nat. Med. 28, 2124–2132 (2022).
Rurik, J. G. et al. Science 375, 91–96 (2022).
Amor, C. et al. Nature 583, 127–132 (2020).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
P.B. declares no financial interests. J.F. is listed as co-inventor of several patents on CAR technologies unrelated to the subject matter of this study.
Rights and permissions
About this article
Cite this article
Bucher, P., Feucht, J. LINKing signaling domains to enhance CAR T cells. Nat Cancer 4, 447–449 (2023). https://doi.org/10.1038/s43018-023-00538-7
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s43018-023-00538-7
This article is cited by
-
Advancing cancer gene therapy: the emerging role of nanoparticle delivery systems
Journal of Nanobiotechnology (2025)