Open Access

Science

, volume 386 , issue 6726

Programming tissue-sensing T cells that deliver therapies to the brain

Milos S Simic ¹

Payal Watchmaker ²

Sasha Gupta ³

Yuan Wang ^{4, 5}

Sharon A. Sagan ³

Jason Duecker ¹

Chanelle Shepherd ¹

David Diebold ²

Psalm Pineo-Cavanaugh ²

Jeffrey Haegelin ²

Robert Zhu ¹

Ben Ng ¹

Wei Yu ¹

Yurie Tonai ¹

Lia Cardarelli ⁶

Nishith R. Reddy ¹

Sachdev S. Sidhu ⁶

Olga G. Troyanskaya ^{4, 5, 7}

Stephen L. Hauser ³

Michael R. Wilson ³

S. Zamvil ^{3, 8}

Hideho Okada ^{2, 9, 10}

Wendell A Lim ^{1, 9}

Hide authors affiliations Show authors affiliations: 10 affiliations

UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA. |

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. |

Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. |

⁴

Department of Computer Science, Princeton University, Princeton, NJ, USA. |

⁵

Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA. |

⁶

School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada. |

⁷

Center for Computational Biology, Flatiron Institute, New York, NY, USA. |

⁸

Program in Immunology, University of California San Francisco, San Francisco, CA, USA. |

⁹

Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. |

¹⁰

Helen Diller Cancer Center, University of California San Francisco, San Francisco, CA, USA. |

Publication type: Journal Article

Publication date: 2024-12-06

American Association for the Advancement of Science (AAAS)

Science

scimago Q1

wos Q1

SJR: 10.416

CiteScore: 48.4

Impact factor: 45.8

ISSN: 00368075, 10959203

DOI: 10.1126/science.adl4237

Copy DOI

PubMed ID: 39636984

Abstract

To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain. CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation. Tissue-sensing cells represent a strategy for addressing diverse disorders in an anatomically targeted manner.

Found

Top-30

Journals

	1 2 3
Frontiers in Immunology	Frontiers in Immunology, 3, 6.38% Frontiers in Immunology 3 publications, 6.38%
Science	Science, 2, 4.26% Science 2 publications, 4.26%
Molecular Therapy	Molecular Therapy, 2, 4.26% Molecular Therapy 2 publications, 4.26%
npj Precision Oncology	npj Precision Oncology, 2, 4.26% npj Precision Oncology 2 publications, 4.26%
Journal of Translational Medicine	Journal of Translational Medicine, 2, 4.26% Journal of Translational Medicine 2 publications, 4.26%
Advanced Science	Advanced Science, 2, 4.26% Advanced Science 2 publications, 4.26%
Biomaterials	Biomaterials, 2, 4.26% Biomaterials 2 publications, 4.26%
Cell Reports Medicine	Cell Reports Medicine, 2, 4.26% Cell Reports Medicine 2 publications, 4.26%
Nature	Nature, 1, 2.13% Nature 1 publication, 2.13%
Materials Today Bio	Materials Today Bio, 1, 2.13% Materials Today Bio 1 publication, 2.13%
Nature Reviews Drug Discovery	Nature Reviews Drug Discovery, 1, 2.13% Nature Reviews Drug Discovery 1 publication, 2.13%
Trends in Immunology	Trends in Immunology, 1, 2.13% Trends in Immunology 1 publication, 2.13%
InFo Neurologie + Psychiatrie	InFo Neurologie + Psychiatrie, 1, 2.13% InFo Neurologie + Psychiatrie 1 publication, 2.13%
Cancer Cell	Cancer Cell, 1, 2.13% Cancer Cell 1 publication, 2.13%
Seminars in Immunology	Seminars in Immunology, 1, 2.13% Seminars in Immunology 1 publication, 2.13%
American Journal of Physiology - Cell Physiology	American Journal of Physiology - Cell Physiology, 1, 2.13% American Journal of Physiology - Cell Physiology 1 publication, 2.13%
Annals of Neurology	Annals of Neurology, 1, 2.13% Annals of Neurology 1 publication, 2.13%
Science advances	Science advances, 1, 2.13% Science advances 1 publication, 2.13%
European Journal of Pharmaceutics and Biopharmaceutics	European Journal of Pharmaceutics and Biopharmaceutics, 1, 2.13% European Journal of Pharmaceutics and Biopharmaceutics 1 publication, 2.13%
Brain, Behavior, and Immunity	Brain, Behavior, and Immunity, 1, 2.13% Brain, Behavior, and Immunity 1 publication, 2.13%
Advanced Materials	Advanced Materials, 1, 2.13% Advanced Materials 1 publication, 2.13%
Cancer Communications	Cancer Communications, 1, 2.13% Cancer Communications 1 publication, 2.13%
Medicina	Medicina, 1, 2.13% Medicina 1 publication, 2.13%
Discover Oncology	Discover Oncology, 1, 2.13% Discover Oncology 1 publication, 2.13%
Human Vaccines and Immunotherapeutics	Human Vaccines and Immunotherapeutics, 1, 2.13% Human Vaccines and Immunotherapeutics 1 publication, 2.13%
Regenerative Engineering and Translational Medicine	Regenerative Engineering and Translational Medicine, 1, 2.13% Regenerative Engineering and Translational Medicine 1 publication, 2.13%
Journal of Controlled Release	Journal of Controlled Release, 1, 2.13% Journal of Controlled Release 1 publication, 2.13%
Nature Reviews Immunology	Nature Reviews Immunology, 1, 2.13% Nature Reviews Immunology 1 publication, 2.13%
Seminars in Oncology	Seminars in Oncology, 1, 2.13% Seminars in Oncology 1 publication, 2.13%
	1 2 3

Publishers

	2 4 6 8 10 12 14 16
Elsevier	Elsevier, 15, 31.91% Elsevier 15 publications, 31.91%
Springer Nature	Springer Nature, 11, 23.4% Springer Nature 11 publications, 23.4%
Wiley	Wiley, 5, 10.64% Wiley 5 publications, 10.64%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 4, 8.51% Cold Spring Harbor Laboratory 4 publications, 8.51%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 3, 6.38% American Association for the Advancement of Science (AAAS) 3 publications, 6.38%
Frontiers Media S.A.	Frontiers Media S.A., 3, 6.38% Frontiers Media S.A. 3 publications, 6.38%
American Physiological Society	American Physiological Society, 1, 2.13% American Physiological Society 1 publication, 2.13%
Institute of Electrical and Electronics Engineers (IEEE)	Institute of Electrical and Electronics Engineers (IEEE), 1, 2.13% Institute of Electrical and Electronics Engineers (IEEE) 1 publication, 2.13%
MDPI	MDPI, 1, 2.13% MDPI 1 publication, 2.13%
Taylor & Francis	Taylor & Francis, 1, 2.13% Taylor & Francis 1 publication, 2.13%
AIP Publishing	AIP Publishing, 1, 2.13% AIP Publishing 1 publication, 2.13%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 2.13% Public Library of Science (PLoS) 1 publication, 2.13%
	2 4 6 8 10 12 14 16

We do not take into account publications without a DOI.
Statistics recalculated weekly.

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.

PDF

Metrics

Cite this

GOST |

Cite this

GOST Copy

Simic M. S. et al. Programming tissue-sensing T cells that deliver therapies to the brain // Science. 2024. Vol. 386. No. 6726.

GOST all authors (up to 50) Copy

Simic M. S., Watchmaker P., Gupta S., Wang Y., Sagan S. A., Duecker J., Shepherd C., Diebold D., Pineo-Cavanaugh P., Haegelin J., Zhu R., Ng B., Yu W., Tonai Y., Cardarelli L., Reddy N. R., Sidhu S. S., Troyanskaya O. G., Hauser S. L., Wilson M. R., Zamvil S., Okada H., Lim W. A. Programming tissue-sensing T cells that deliver therapies to the brain // Science. 2024. Vol. 386. No. 6726.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1126/science.adl4237

UR - https://www.science.org/doi/10.1126/science.adl4237

TI - Programming tissue-sensing T cells that deliver therapies to the brain

T2 - Science

AU - Simic, Milos S

AU - Watchmaker, Payal

AU - Gupta, Sasha

AU - Wang, Yuan

AU - Sagan, Sharon A.

AU - Duecker, Jason

AU - Shepherd, Chanelle

AU - Diebold, David

AU - Pineo-Cavanaugh, Psalm

AU - Haegelin, Jeffrey

AU - Zhu, Robert

AU - Ng, Ben

AU - Yu, Wei

AU - Tonai, Yurie

AU - Cardarelli, Lia

AU - Reddy, Nishith R.

AU - Sidhu, Sachdev S.

AU - Troyanskaya, Olga G.

AU - Hauser, Stephen L.

AU - Wilson, Michael R.

AU - Zamvil, S.

AU - Okada, Hideho

AU - Lim, Wendell A

PY - 2024

DA - 2024/12/06

PB - American Association for the Advancement of Science (AAAS)

IS - 6726

VL - 386

PMID - 39636984

SN - 0036-8075

SN - 1095-9203

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2024_Simic,

author = {Milos S Simic and Payal Watchmaker and Sasha Gupta and Yuan Wang and Sharon A. Sagan and Jason Duecker and Chanelle Shepherd and David Diebold and Psalm Pineo-Cavanaugh and Jeffrey Haegelin and Robert Zhu and Ben Ng and Wei Yu and Yurie Tonai and Lia Cardarelli and Nishith R. Reddy and Sachdev S. Sidhu and Olga G. Troyanskaya and Stephen L. Hauser and Michael R. Wilson and S. Zamvil and Hideho Okada and Wendell A Lim},

title = {Programming tissue-sensing T cells that deliver therapies to the brain},

journal = {Science},

year = {2024},

volume = {386},

publisher = {American Association for the Advancement of Science (AAAS)},

month = {dec},

url = {https://www.science.org/doi/10.1126/science.adl4237},

number = {6726},

doi = {10.1126/science.adl4237}

}

Publisher

American Association for the Advancement of Science (AAAS)

Journal

Science

scimago Q1

wos Q1

SJR

10.416

CiteScore

48.4

Impact factor

45.8

ISSN

00368075 (Print)

10959203 (Electronic)