Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells.

Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Research Abstract Details 

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Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Abstract Text:

Yu Zhou,Daryl C Drummond,Hao Zou,Mark E Hayes,Gregory P Adams,Dmitri B Kirpotin,James D Marks,

To determine the importance of single-chain Fv (scFv) affinity on binding, uptake, and cytotoxicity of tumor-targeting nanoparticles, the affinity of the epidermal growth factor receptor (EGFR) scFv antibody C10 was increased using molecular evolution and yeast display. A library containing scFv mutants was created by error-prone PCR, displayed on the surface of yeast, and higher affinity clones selected by fluorescence activated cell sorting. Ten mutant scFv were identified that had a 3-18-fold improvement in affinity (KD=15-88 nM) for EGFR-expressing A431 tumor cells compared to C10 scFv (KD=264 nM). By combining mutations, higher affinity scFv were generated with KD ranging from 0.9 nM to 10 nM. The highest affinity scFv had a 280-fold higher affinity compared to that of the parental C10 scFv. Immunoliposome nanoparticles (ILs) were prepared using EGFR scFv with a 280-fold range of affinities, and their binding and uptake into EGFR-expressing tumor cells was quantified. At scFv densities greater than 148 scFv/IL, there was no effect of scFv affinity on IL binding and uptake into tumor cells, or on cytotoxicity. At lower scFv densities, there was less uptake and binding for ILs constructed from the very low affinity C10 scFv. The results show the importance of antibody fragment density on nanoparticle uptake, and suggest that engineering ultrahigh affinity scFv may be unnecessary for optimal nanoparticle targeting.

Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Publishing Authors By Initials

Y Zhou,DC Drummond,H Zou,ME Hayes,GP Adams,DB Kirpotin,JD Marks,

For similar heterocyclic compounds: alkaloids: camptothecin: topotecan research abstracts see: heterocyclic compounds: alkaloids: camptothecin: topotecan research

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Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of molecular biology

VOLUME: 371

Page Numbers: 934-47

Journal Abbreviation: J. Mol. Biol.

ISSN: 0022-2836

DAY: 10

MONTH: 05

YEAR: 2007

Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Information

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LANGUAGE: eng

NlmUniqueID: 2985088

Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Keywords Mesh Terms:

KEYWORDS: Topotecan

MESH TERMS: toxicity

Chemical & Substance for Abstract: Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. Information

Substance Name: Receptor, Epidermal Growth Factor

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells.

AFFILIATION: Department of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco Rm 3C-38, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA.

Country: England

AGENCY: United States NCI

GRANT: P50-CA58207

ACRONYM: CA

MEDLINETA: J Mol Biol

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