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Cited by 268

The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.

In Vivo mRNA CAR T Cell Engineering via Targeted Ionizable Lipid Nanoparticles with Extrahepatic Tropism

Billingsley, Margaret M., Gong, Ningqiang, Mukalel, Alvin J., Thatte, Ajay S., El‐Mayta, Rakan, Patel, Savan K., Metzloff, Ann E., Swingle, Kelsey L., Han, Xuexiang, Xue, Lulu, Hamilton, Alex G., Safford, Hannah C., Alameh, Mohamad‐Gabriel, Papp, Tyler E., Parhiz, Hamideh, Weissman, Drew, Mitchell, Michael J.·2024·Small
DOI 10.1002/smll.202304378
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Abstract

With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these therapies rely on ex vivo viral transduction to induce permanent CAR expression in T cells, which contributes to high production costs and long‐term side effects. Thus, this work aims to develop an in vivo CAR T cell engineering platform to streamline production while using mRNA to induce transient, tunable CAR expression. Specifically, an ionizable lipid nanoparticle (LNP) is utilized as these platforms have demonstrated clinical success in nucleic acid delivery. Though LNPs often accumulate in the liver, the LNP platform used here achieves extrahepatic transfection with enhanced delivery to the spleen, and it is further modified via antibody conjugation (Ab‐LNPs) to target pan‐T cell markers. The in vivo evaluation of these Ab‐LNPs confirms that targeting is necessary for potent T cell transfection. When using these Ab‐LNPs for the delivery of CAR mRNA, antibody and dose‐dependent CAR expression and cytokine release are observed along with B cell depletion of up to 90%. In all, this work conjugates antibodies to LNPs with extrahepatic tropism, evaluates pan‐T cell markers, and develops Ab‐LNPs capable of generating functional CAR T cells in vivo.

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Metadata

Authors
Billingsley, M. M., Gong, N., Mukalel, A. J., Thatte, A. S., El‐Mayta, R., Patel, S. K., Metzloff, A. E., Swingle, K. L., Han, X., Xue, L., Hamilton, A. G., Safford, H. C., Alameh, M., Papp, T. E., Parhiz, H., Weissman, D., & Mitchell, M. J.
Venue
Small
Publisher
Wiley
Published
2023-12-10
Volume
20
Issue
11
Pages
e2304378-e2304378
ISSN
  • 1613-6810 (ISSN-L)
  • 1613-6829
DOI
10.1002/smll.202304378
OpenAlex
W4389527549
Cited by
268
References
80
FWCI
20.02
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: In Vivo mRNA CAR T Cell Engineering via Targeted Ionizable Lipid Nanoparticles with Extrahepatic Tropism. https://app.cochat.ai/papers/10.1002/smll.202304378
The paper
Billingsley, M. M., Gong, N., Mukalel, A. J., Thatte, A. S., El‐Mayta, R., Patel, S. K., Metzloff, A. E., Swingle, K. L., Han, X., Xue, L., Hamilton, A. G., Safford, H. C., Alameh, M., Papp, T. E., Parhiz, H., Weissman, D., & Mitchell, M. J. (2024). In Vivo mRNA CAR T Cell Engineering via Targeted Ionizable Lipid Nanoparticles with Extrahepatic Tropism. Small. https://doi.org/10.1002/smll.202304378

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.