Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

Anne Selch Tvilum; Mikkel Illemann Johansen; Lærke Nøhr Glud; Diana Malskær Ivarsen; Amanda Batoul Khamas; Sheiliza Carmali; Snehit Satish Mhatre; Ane Bretschneider Søgaard; Emma Faddy; Lisanne de Vor; Suzan H. M. Rooijakkers; Lars Jørgen Østergaard; Nis Pedersen Jørgensen; Rikke Louise Meyer; Alexander Zelikin

doi:10.1002/advs.202301340

Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

Anne Selch Tvilum, Mikkel Illemann Johansen, Lærke Nøhr Glud, Diana Malskær Ivarsen, Amanda Batoul Khamas, Sheiliza Carmali, Snehit Satish Mhatre, Ane Bretschneider Søgaard, Emma Faddy, Lisanne de Vor, Suzan H. M. Rooijakkers, Lars Jørgen Østergaard, Nis Pedersen Jørgensen^*, Rikke Louise Meyer^*, Alexander Zelikin^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

10 Citationer (Scopus)

Abstract

The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.

Originalsprog	Engelsk
Artikelnummer	2301340
Tidsskrift	Advanced Science
Vol/bind	10
Nummer	23
Antal sider	15
ISSN	2198-3844
DOI	https://doi.org/10.1002/advs.202301340
Status	Udgivet - aug. 2023

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10.1002/advs.202301340Licens: CC BY

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Tvilum, A. S., Johansen, M. I., Glud, L. N., Ivarsen, D. M., Khamas, A. B., Carmali, S., Mhatre, S. S., Søgaard, A. B., Faddy, E., de Vor, L., H. M. Rooijakkers, S., Østergaard, L. J., Jørgensen, N. P., Meyer, R. L., & Zelikin, A. (2023). Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release. Advanced Science, 10(23), Artikel 2301340. https://doi.org/10.1002/advs.202301340

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title = "Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release",

abstract = "The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.",

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year = "2023",

month = aug,

doi = "10.1002/advs.202301340",

language = "English",

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number = "23",

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Tvilum, AS, Johansen, MI, Glud, LN, Ivarsen, DM, Khamas, AB, Carmali, S, Mhatre, SS, Søgaard, AB , Faddy, E, de Vor, L, H. M. Rooijakkers, S, Østergaard, LJ , Jørgensen, NP , Meyer, RL & Zelikin, A 2023, 'Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release', Advanced Science, bind 10, nr. 23, 2301340. https://doi.org/10.1002/advs.202301340

TY - JOUR

T1 - Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

AU - Tvilum, Anne Selch

AU - Johansen, Mikkel Illemann

AU - Glud, Lærke Nøhr

AU - Ivarsen, Diana Malskær

AU - Khamas, Amanda Batoul

AU - Carmali, Sheiliza

AU - Mhatre, Snehit Satish

AU - Søgaard, Ane Bretschneider

AU - Faddy, Emma

AU - de Vor, Lisanne

AU - H. M. Rooijakkers, Suzan

AU - Østergaard, Lars Jørgen

AU - Jørgensen, Nis Pedersen

AU - Meyer, Rikke Louise

AU - Zelikin, Alexander

PY - 2023/8

Y1 - 2023/8

N2 - The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.

AB - The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.

KW - antibody-drug-conjugates

KW - antimicrobials

KW - biofilms

KW - drug targeting

KW - Animals

KW - Biofilms

KW - Immunoconjugates

KW - Drug Liberation

KW - Bacteria

KW - Mice

KW - Anti-Infective Agents

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U2 - 10.1002/advs.202301340

DO - 10.1002/advs.202301340

M3 - Journal article

C2 - 37290045

SN - 2198-3844

VL - 10

JO - Advanced Science

JF - Advanced Science

IS - 23

M1 - 2301340

ER -

Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

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