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 for this work

University of Copenhagen

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	391
Journal	Molecules
Volume	30
Issue number	2
Number of pages	12
ISSN	1420-3049
DOIs	https://doi.org/10.3390/molecules30020391
Publication status	Published - 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Breast cancer
Targeted treatment
Nanobody
Site-selective conjugation

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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.",

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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

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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 - Targeted treatment

KW - Nanobody

KW - Site-selective conjugation

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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Keywords

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