The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Anti-HER2 scFv-Directed Extracellular Vesicle-Mediated mRNA-Based Gene Delivery Inhibits Growth of HER2-Positive Human Breast Tumor Xenografts by Prodrug Activation
Open accessPublished version of a preprint
Abstract
This paper deals with specific targeting of the prodrug/enzyme regimen, CNOB/HChrR6, to treat a serious disease, namely HER2+ human breast cancer with minimal off-target toxicity. HChrR6 is an improved bacterial enzyme that converts CNOB into the cytotoxic drug MCHB. Extracellular vesicles (EV) were used for mRNA-based HchrR6 gene delivery: EVs may cause minimal immune rejection, and mRNA may be superior to DNA for gene delivery. To confine HChrR6 generation and CNOB activation to the cancer, the EVHB chimeric protein was constructed. It contains high-affinity anti-HER2 scFv antibody (ML39) and is capable of latching on to EV surface. Cells transfected with EVHB-encoding plasmid generated EVs displaying this protein (“directed EVs”). Transfection of a separate batch of cells with the new plasmid, XPort/HChrR6, generated EVs containing HChrR6 mRNA; incubation with pure EVHB enabled these to target the HER2 receptor, generating “EXO-DEPT” EVs. EXO-DEPT treatment specifically enabled HER2-overexpressing BT474 cells to convert CNOB into MCHB in actinomycin D–independent manner, showing successful and specific delivery of HChrR6 mRNA. EXO-DEPTs—but not undirected EVs—plus CNOB caused near-complete growth arrest of orthotopic BT474 xenografts in vivo, demonstrating for the first time EV-mediated delivery of functional exogenous mRNA to tumors. EXO-DEPTs may be generated from patients' own dendritic cells to evade immune rejection, and without plasmids and their potentially harmful genetic material, raising the prospect of clinical use of this regimen. This approach can be used to treat any disease overexpressing a specific marker. Mol Cancer Ther; 17(5); 1133–42. ©2018 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As a result, the growth of BT474 xenografts was almost completely arrested after the prodrug treatment [123].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [123]
In the citing paper
“In vivo, administration of these engineered exosomes resulted in the efficient expression of HChrR6 in tumor cells.”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [123]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760
The Phyre2 web portal for protein modeling, prediction and analysis
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015) · Nature Protocols · doi:10.1038/nprot.2015.053 · Cited by 9,652
Untangling the ErbB signalling network
Yarden, Y., & Sliwkowski, M. X. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052073 · Cited by 6,974
Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer
Slamon, D. J., Godolphin, W. J., Jones, L. A., Holt, J. A., Wong, S., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J. A., Ullrich, A., et al. (1989) · Science · doi:10.1126/science.2470152 · Cited by 6,817
Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
Colombo, M., Raposo, G., & Théry, C. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122326 · Cited by 6,186
Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer
Romond, E. H., Perez, E. A., Bryant, J., Suman, V. J., Geyer, C. E., Davidson, N. E., Tan-Chiu, E., Martino, S., Paik, S., Kaufman, P. A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa052122 · Cited by 5,438
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930
Trastuzumab-Induced Hepatotoxicity: A Case Report
Vucicevic, D., Carey, E. J., & Karlin, N. J. (2013) · Breast Care · doi:10.1159/000346844 · Cited by 4,432
Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Geyer, C. E., Forster, J. K., Lindquist, D. L., Chan, S. Y. T., Romieu, C. G., Pieńkowski, T., Jagiełło-Gruszfeld, A., Crown, J. P., Chan, A., Kaufman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa064320 · Cited by 3,458
Adjuvant Trastuzumab in HER2-Positive Breast Cancer
Slamon, D. J., EIERMANN, W., Robert, N. J., Pieńkowski, T., Martín, M., Press, M. F., Mackey, J. R., Glaspy, J. A., Chan, A., Pawlicki, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa0910383 · Cited by 2,833
Cited by
Sorted by citations
Context-specific regulation of extracellular vesicle biogenesis and cargo selection
Dixson, A. C., Dawson, T. R., Vizio, D. D., & Weaver, A. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00576-0 · Cited by 847
Therapeutically harnessing extracellular vesicles
Cheng, L., & Hill, A. F. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00410-w · Cited by 737
Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking
Murphy, D. E., de Jong, O. G., Brouwer, M., Wood, M. J. A., Lavieu, G., Schiffelers, R. M., & Vader, P. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0223-5 · Cited by 740
Liang, G., Zhu, Y., Ali, D. J., Tian, T., Xu, H., Si, K., Sun, B., Chen, B., & Xiao, Z. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-019-0563-2 · Cited by 619
Salunkhe, S. A., Dheeraj, Basak, M., Chitkara, D., & Mittal, A. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.07.042 · Cited by 513
Metadata
- Authors
- Wang, J.-H., Forterre, A. V., Zhao, J., Frimannsson, D. O., Delcayre, A., Antes, T. J., Efron, B., Jeffrey, S. S., Pegram, M. D., & Matin, A. C.
- Affiliations
- Stanford Medicine (US)
- 2ExoThera LLC, Menlo Park, California.
- System Biosciences (United States) (US)
- Stanford University (US)
- Corresponding author
- Matin, A.C.
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2018-04-30
- Volume
- 17
- Issue
- 5
- Pages
- 1133-1142
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC5932266
- OpenAlex
- W2792159629
- Cited by
- 181
- References
- 67
- Citations by year
- 2026: 12 · 2025: 28 · 2024: 33 · 2023: 29 · 2022: 26 · 2021: 17 · 2020: 16 · 2019: 15 · 2018: 5
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (UH3TR000902)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- HER2-positive breast cancer, extracellular vesicles, prodrug activation, fusion protein, targeted drug delivery, BT474 xenograft, tumor growth inhibition
- MeSH terms
- Extracellular Vesicles, Animals, Breast Neoplasms, Female, Humans, Mice, Inbred BALB C, Mice, Nude, Oxazines, Prodrugs, RNA, Messenger, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Single-Chain Antibodies, MCF-7 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
