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Development of anti-p185HER2 immunoliposomes for cancer therapy.
Open accessAbstract
The product of the HER2 protooncogene, p185HER2, represents an attractive target for cancer immunotherapies. We have prepared anti-p185HER2 immunoliposomes in which Fab' fragments of a humanized anti-p185HER2 monoclonal antibody with antiproliferative properties (rhuMAb-HER2) were conjugated to either conventional or sterically stabilized liposomes. These immunoliposomes bind specifically to p185HER2-overexpressing breast cancer cells (SK-BR-3 and BT-474). High-affinity binding of anti-p185HER2 immunoliposomes is comparable to that of free rhuMAbHER2-Fab' or the intact antibody. Empty immunoliposomes inhibit the culture growth of p185HER2-overexpressing breast cancer cells, and this antiproliferative effect is superior to that of free rhuMAbHER2-Fab', indicating that liposomal anchoring of these anti-p185HER2 Fab' fragments enhances their biological activity. Efficient internalization of anti-p185HER2 immunoliposomes, demonstrated by light and electron microscopy, occurs by receptor-mediated endocytosis via the coated pit pathway and also possibly by membrane fusion. Doxorubicin-loaded anti-p185HER2 immunoliposomes are markedly and specifically cytotoxic against p185HER2-overexpressing tumor cells in vitro. Anti-p185HER2 immunoliposomes administered in vivo in Scid mice bearing human breast tumor (BT-474) xenografts can deliver doxorubicin to tumors. These results indicate that anti-p185HER2 immunoliposomes are a promising therapeutic vehicle for the treatment of p185HER2-overexpressing human cancers.
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Citations
Cited by
Liposome application: problems and prospects.
Barenholz, Y. (2001) · Current Opinion in Colloid & Interface Science · doi:10.1016/s1359-0294(00)00090-x · Cited by 659
Passive and Active Drug Targeting: Drug Delivery to Tumors as an Example
Torchilin, V. P. (2010) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-00477-3_1 · Cited by 573
Liposome-based drug delivery in breast cancer treatment
Park, J. W. (2002) · Breast Cancer Research · doi:10.1186/bcr432 · Cited by 469
Self-citationLigand-targeted liposomal anticancer drugs
Sapra, P., & Allen, T. M. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(03)00032-8 · Cited by 438
Formulation and delivery issues for monoclonal antibody therapeutics
Daugherty, A. L., & Mrsny, R. J. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.03.011 · Cited by 351
Metadata
- Authors
- Park, J. W., Hong, K., Carter, P., Asgari, H., Guo, L. Y., Keller, G. A., Wirth, C., Shalaby, R., Kotts, C., & Wood, W. I.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-02-28
- Volume
- 92
- Issue
- 5
- Pages
- 1327-1331
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2137155864
- Cited by
- 258
- References
- 0
- FWCI
- 14.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Park, J. W., Hong, K., Carter, P., Asgari, H., Guo, L. Y., Keller, G. A., Wirth, C., Shalaby, R., Kotts, C., & Wood, W. I. (1995). Development of anti-p185HER2 immunoliposomes for cancer therapy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.92.5.1327
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