Details:

Alternative Title:
Angew Chem Int Ed Engl
Publisher's site:
http://dx.doi.org/10.1002/anie.201509432
Personal Author:
Fang, Tao ; Duarte, Joao N. ; Ling, Jingjing ; Li, Zeyang ; Guzman, Jonathan S. ; ... More +
Fang, Tao ; Duarte, Joao N. ; Ling, Jingjing ; Li, Zeyang ; Guzman, Jonathan S. ; Ploegh, Hidde L. ; Less -
Description:
Antibody-drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but further advances are constrained by the complex structures of full-sized antibodies. Camelid-derived single-domain antibody fragments (VHHs or nanobodies) offer a possible solution to this challenge by providing expedited target screening and validation through switching between imaging and therapeutic activities. We used a nanobody (VHH7) specific for murine MHC-II and rendered "sortase-ready" for the introduction of oligoglycine-modified cytotoxic payloads or NIR fluorophores. The VHH7 conjugates outcompeted commercial monoclonal antibodies (mAbs) for internalization and exhibited high specificity and cytotoxicity against A20 murine B-cell lymphoma. Non-invasive NIR imaging with a VHH7-fluorophore conjugate showed rapid tumor targeting on both localized and metastatic lymphoma models. Subsequent treatment with the nanobody-drug conjugate efficiently controlled tumor growth and metastasis without obvious systemic toxicity.
Subject:
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Animals
Antibody–drug Conjugates
Antineoplastic Agents
Article
Cancer
Cell Line, Tumor
Histocompatibility Antigens Class II
Humans
Lymphoma, B-Cell
Mice
Nanobody
Single-Domain Antibodies
Sortase

Source:
Angew Chem Int Ed Engl. 55(7):2416-2420. ;
Pubmed ID:
26840214
Pubmed Central ID:
PMC4820396
Document Type:
Journal Article ;
Funding:
DP1 GM106409/GM/NIGMS NIH HHS/United States ; R01 AI087879/AI/NIAID NIH HHS/United States ; DP1 GM106409/DP/NCCDPHP CDC HHS/United States ; R01AI087879/AI/NIAID NIH HHS/United States ;
DP1 GM106409/GM/NIGMS NIH HHS/United States ; R01 AI087879/AI/NIAID NIH HHS/United States ; DP1 GM106409/DP/NCCDPHP CDC HHS/United States ; R01AI087879/AI/NIAID NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:9055ea9f6b63070d103a849d2e68462b73d8fc05a875a91418d0fe77a949c8e8
File Type:

Supporting Files

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