Unknown

Dataset Information

0

Structurally Defined ?MHC-II Nanobody-Drug Conjugates: A Therapeutic and Imaging System for B-Cell Lymphoma.


ABSTRACT: 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.

SUBMITTER: Fang T 

PROVIDER: S-EPMC4820396 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structurally Defined αMHC-II Nanobody-Drug Conjugates: A Therapeutic and Imaging System for B-Cell Lymphoma.

Fang Tao T   Duarte Joao N JN   Ling Jingjing J   Li Zeyang Z   Guzman Jonathan S JS   Ploegh Hidde L HL  

Angewandte Chemie (International ed. in English) 20160114 7


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  ...[more]

Similar Datasets

| S-EPMC7261152 | biostudies-literature
| S-EPMC8111546 | biostudies-literature
| S-EPMC6593736 | biostudies-literature
| S-EPMC1200880 | biostudies-literature
| S-EPMC4427876 | biostudies-literature
| S-EPMC4891273 | biostudies-literature
| S-EPMC9240879 | biostudies-literature
| S-EPMC6030498 | biostudies-literature
| S-EPMC9972495 | biostudies-literature
| S-EPMC4028821 | biostudies-literature