Targeted cellular micropharmacies deliver therapeutic agents to the brain.
Overview
- Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center,New York, NY USA
- Present Address: R&D Protein Engineering & Novel Modalities; Biologics Engineering, AstraZeneca,1 MedImmune Way, Gaithersburg, MD USA
- Gerstner Sloan Kettering Graduate School, Memorial Sloan-Kettering Cancer Center,New York, NY USA
- Chemical Biology Program, Memorial Sloan-Kettering Cancer Center,New York, NY USA
- Program in Neurosciences, Weill Graduate School of Medical Sciences of Cornell University,New York, NY USA
- Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center,New York, NY USA
- Tri-institutional Program in Chemical Biology Weill Graduate School of Medical Sciences of Cornell University,New York, NY USA
- Program in Pharmacology, Weill Graduate School of Medical Sciences of Cornell University,New York, NY USA
Abstract
The systemic administration of therapeutic agents, particularly large, charged molecules such as antibodies, has limited efficacy in treating central nervous system (CNS) disorders. In addition, the slow progression of neurodegenerative diseases makes repeated intrathecal injections unfeasible. Alzheimer’s disease is characterized by the accumulation of Aβ amyloid plaques. Microglia contribute to the clearance of Aβ, but are inhibited by the expression of CD33. Therefore, antibody blocking of CD33 may enhance the phagocytosis of Aβ by microglial cells, slowing AD progression. Here, we use cells as “targeted cellular micropharmacies” that are retained in the CNS to deliver therapeutic proteins directly into the brain. To achieve this, we genetically engineered CD4 T-cells to express: (1) a chimeric antigen receptor against GD2 to retain the cells in the brain, (2) ectopic FoxP3 to reduce inflammation, (3) secreted IL-2 to promote cell longevity, and (4) secreted anti-CD33 scFv antibody. Our proof-of-concept demonstrates that therapeutic antibodies can be delivered to the brain for at least 8 weeks to treat neurological disorders. Other agents could be similarly delivered into the brain by this platform.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
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Data
Datasets cited
- biostudies:S-BSST2770, at BioStudies; found in “Data availability”
- geo:GSE321698, at NCBI GEO; found in “Data availability”
Other data links
- ebi.ac.uk/
biostudies/ , EMBL-EBI; found in the notessourcedata
Data availability
Source data for Figs. 1–6 have been provided. Specifically, source data for Figs. 1, 3, 4, and 6 are available in the following database: BioStudies S-BSST2770 (http://
The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_103
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 3 keywords, 11 MeSH terms, 11 funders, 71 references, 1 RRID.
Cite
This paper
Malviya, M., Baniya, S., Wong, E., Jain, T., Manoranjan, B., Vogt, K. C., Kehs, Z., Silberman, P. C., Dao, T., Li, Y., & Scheinberg, D. A. (2026). Targeted cellular micropharmacies deliver therapeutic agents to the brain. EMBO molecular medicine, 18(6), 2455-2482. https://
BibTeX
@article{malviya2026targ
author = {Malviya, Manish and Baniya, Subha and Wong, Eitan and Jain, Tanya and Manoranjan, Branavan and Vogt, Kristen C and Kehs, Zoe and Silberman, Pedro C and Dao, Tao and Li, Yueming and Scheinberg, David A},
title = {{Targeted cellular micropharmacies deliver therapeutic agents to the brain}},
journal = {EMBO molecular medicine},
year = {2026},
month = apr,
volume = {18},
number = {6},
pages = {2455--2482},
publisher = {Nature Publishing Group},
issn = {1757-4676},
doi = {10.1038/
url = {https://
pmid = {41981294},
pmcid = {PMC13270026}
}
RIS
TY - JOUR
AU - Malviya, Manish
AU - Baniya, Subha
AU - Wong, Eitan
AU - Jain, Tanya
AU - Manoranjan, Branavan
AU - Vogt, Kristen C
AU - Kehs, Zoe
AU - Silberman, Pedro C
AU - Dao, Tao
AU - Li, Yueming
AU - Scheinberg, David A
TI - Targeted cellular micropharmacies deliver therapeutic agents to the brain
T2 - EMBO molecular medicine
J2 - EMBO Mol Med
PY - 2026
DA - 2026/
VL - 18
IS - 6
SP - 2455
EP - 2482
SN - 1757-4676
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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