A HER2 Specific Nanobody-Drug Conjugate: Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models

Anders H Hansen; Kasper I H Andersen; Li Xin; Oliver Krigslund; Niels Behrendt; Lars H Engelholm; Claus H Bang-Bertelsen; Sanne Schoffelen; Katrine Qvortrup

doi:10.3390/molecules30020391

A HER2 Specific Nanobody-Drug Conjugate: Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models

Anders H Hansen
, Kasper I H Andersen
, Li Xin
, Oliver Krigslund
, Niels Behrendt
, Lars H Engelholm
, Claus H Bang-Bertelsen
, Sanne Schoffelen
, Katrine Qvortrup^*

^*Corresponding author af dette arbejde

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4 Citationer (Scopus)

Abstract

A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.

Originalsprog	Engelsk
Artikelnummer	391
Tidsskrift	Molecules
Vol/bind	30
Udgave nummer	2
ISSN	1420-3049
DOI	https://doi.org/10.3390/molecules30020391
Status	Udgivet - 18 jan. 2025

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10.3390/molecules30020391Licens: CC BY

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title = "A HER2 Specific Nanobody-Drug Conjugate: Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models",

abstract = "A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.",

keywords = "breast cancer, nanobody, site-selective conjugation, targeted treatment",

author = "Hansen, \{Anders H\} and Andersen, \{Kasper I H\} and Li Xin and Oliver Krigslund and Niels Behrendt and Engelholm, \{Lars H\} and Bang-Bertelsen, \{Claus H\} and Sanne Schoffelen and Katrine Qvortrup",

year = "2025",

month = jan,

day = "18",

doi = "10.3390/molecules30020391",

language = "English",

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TY - JOUR

T1 - A HER2 Specific Nanobody-Drug Conjugate

T2 - Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models

AU - Hansen, Anders H

AU - Andersen, Kasper I H

AU - Xin, Li

AU - Krigslund, Oliver

AU - Behrendt, Niels

AU - Engelholm, Lars H

AU - Bang-Bertelsen, Claus H

AU - Schoffelen, Sanne

AU - Qvortrup, Katrine

PY - 2025/1/18

Y1 - 2025/1/18

N2 - A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.

AB - A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.

KW - breast cancer

KW - nanobody

KW - site-selective conjugation

KW - targeted treatment

UR - https://www.scopus.com/pages/publications/85215767507

U2 - 10.3390/molecules30020391

DO - 10.3390/molecules30020391

M3 - Journal article

C2 - 39860260

SN - 1420-3049

VL - 30

JO - Molecules

JF - Molecules

IS - 2

M1 - 391

ER -

A HER2 Specific Nanobody-Drug Conjugate: Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models

Abstract

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