The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Humanization of an anti-p185HER2 antibody for human cancer therapy.
Open accessAbstract
The murine monoclonal antibody mumAb4D5, directed against human epidermal growth factor receptor 2 (p185HER2), specifically inhibits proliferation of human tumor cells overexpressing p185HER2. However, the efficacy of mumAb4D5 in human cancer therapy is likely to be limited by a human anti-mouse antibody response and lack of effector functions. A "humanized" antibody, humAb4D5-1, containing only the antigen binding loops from mumAb4D5 and human variable region framework residues plus IgG1 constant domains was constructed. Light- and heavy-chain variable regions were simultaneously humanized in one step by "gene conversion mutagenesis" using 311-mer and 361-mer preassembled oligonucleotides, respectively. The humAb4D5-1 variant does not block the proliferation of human breast carcinoma SK-BR-3 cells, which overexpress p185HER2, despite tight antigen binding (Kd = 25 nM). One of seven additional humanized variants designed by molecular modeling (humAb4D5-8) binds the p185HER2 antigen 250-fold and 3-fold more tightly than humAb4D5-1 and mumAb4D5, respectively. In addition, humAb4D5-8 has potency comparable to the murine antibody in blocking SK-BR-3 cell proliferation. Furthermore, humAb4D5-8 is much more efficient in supporting antibody-dependent cellular cytotoxicity against SK-BR-3 cells than mumAb4D5, but it does not efficiently kill WI-38 cells, which express p185HER2 at lower levels.
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Cited by
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Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
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Nanoparticle-mediated cellular response is size-dependent
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Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets
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Adjuvant Trastuzumab in HER2-Positive Breast Cancer
Slamon, D., Eiermann, W., Robert, N., Pienkowski, T., Martin, M., Press, M., Mackey, J., Glaspy, J., Chan, A., Pawlicki, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa0910383 · Cited by 2,775
Metadata
- Authors
- Carter, P., Presta, L., Gorman, C. M., Ridgway, J. B., Henner, D., Wong, W. L., Rowland, A. M., Kotts, C., Carver, M. E., & Shepard, H. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1992-05-15
- Volume
- 89
- Issue
- 10
- Pages
- 4285-4289
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2006174096
- Cited by
- 1,918
- References
- 32
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Carter, P., Presta, L., Gorman, C. M., Ridgway, J. B., Henner, D., Wong, W. L., Rowland, A. M., Kotts, C., Carver, M. E., & Shepard, H. M. (1992). Humanization of an anti-p185HER2 antibody for human cancer therapy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.89.10.4285
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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