The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Generation and testing of clinical-grade exosomes for pancreatic cancer
Open accessAbstract
Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. Here, we report on a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer. We perform studies to determine the shelf life, biodistribution, toxicology profile, and efficacy in combination with chemotherapy to inform future clinical testing of GMP iExosomes. Collectively, this report illustrates the process and feasibility of generating clinical-grade exosomes for various therapies of human diseases.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
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
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., Lee, J. J., & Kalluri, R. (2017) · Nature · doi:10.1038/nature22341 · Cited by 2,639
Self-citationBiogenesis and secretion of exosomes
Kowal, J., Tkach, M., & Théry, C. (2014) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.05.004 · Cited by 1,781
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., et al. (2013) · Nature · doi:10.1038/nature12138 · Cited by 1,683
Ha, D., Yang, N., & Nadithe, V. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.02.001 · Cited by 1,346
Johnsen, K. B., Gudbergsson, J. M., Skov, M. N., Pilgaard, L., Moos, T., & Duroux, M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.005 · Cited by 704
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The biology , function , and biomedical applications of exosomes
Kalluri, R., & LeBleu, V. S. (2020) · Science · doi:10.1126/science.aau6977 · Cited by 10,770
“Clinical-grade MSCderived exosomeswithKras siRNApayload (iExosomes) have been used to treat pancreatic cancer in multiple animal models (28, 35).”
InfluentialSelf-citationRNA delivery by extracellular vesicles in mammalian cells and its applications
O’Brien, K., Breyne, K., Ughetto, S., Laurent, L. C., & Breakefield, X. O. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0251-y · Cited by 1,811
The current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Self-citationChallenges and directions in studying cell–cell communication by extracellular vesicles
van Niel, G., Carter, D. R. F., Clayton, A., Lambert, D. W., Raposo, G., & Vader, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00460-3 · Cited by 1,229
Metadata
- Authors
- Mendt, M., Kamerkar, S., Sugimoto, H., McAndrews, K. M., Wu, C.-C., Gagea, M., Yang, S., Blanko, E. V. R., Peng, Q., Ma, X., Marszalek, J. R., Maitra, A., Yee, C., Rezvani, K., Shpall, E., LeBleu, V. S., & Kalluri, R.
- Venue
- JCI Insight
- Published
- 2018-04-19
- Volume
- 3
- Issue
- 8
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2799422921
- Cited by
- 792
- References
- 7
- FWCI
- 22.76
- Type
- journal article
- Language
- en
- Open access
- gold
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- Mendt, M., Kamerkar, S., Sugimoto, H., McAndrews, K. M., Wu, C.-C., Gagea, M., Yang, S., Blanko, E. V. R., Peng, Q., Ma, X., Marszalek, J. R., Maitra, A., Yee, C., Rezvani, K., Shpall, E., LeBleu, V. S., & Kalluri, R. (2018). Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. https://doi.org/10.1172/jci.insight.99263
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