Javascript must be enabled for the correct page display

Chemoenzymatic dimerization of single domain antibodies for multimodal imaging.

Edens, J.G. (2015) Chemoenzymatic dimerization of single domain antibodies for multimodal imaging. Master's Thesis / Essay, Biology.

[img]
Preview
Text
MasterLS_MBB_2015_JGEdens.pdf - Published Version

Download (2MB) | Preview
[img] Text
toestemming.pdf - Other
Restricted to Backend only

Download (532kB)

Abstract

Camelid derived single domain antibody fragments (VHH) are small sized, have rapid circulatory clearance and great binding specificity. Because immune cells can infiltrate tumors, VHHs specifically binding MHC Class II or CD11b can therefore be utilized for cancer detection and the presence of malignancy. VHHs consist of only a single domain, so their binding affinity may entail constrains compared to the natural bivalent antibodies. During this project a chemoenzymatic dimerization approach was developed to enhance the resemblance of these fragments to natural antibodies. Since the specific binding site of the VHH is positioned away from its C-terminus, C-terminal motif LPETG is utilized for sortagging with a linker, enabling dimerization via biorthogonal click chemistry. This linker also allowed the appending of a fluorophore or 18F, which was used for biological evaluation. The dimers were analyzed with in vitro FACS studies and in vivo two-photon microscopy to obtain an assessment of their binding affinity and compare them with their corresponding monomer. Eventually in vivo PET imaging clearly showed lymphoid organs and engrafted tumors infiltrated by immune cells with significant improvement in signal strength.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:10
Last Modified: 15 Feb 2018 08:10
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/13557

Actions (login required)

View Item View Item