Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release-Reference-Cited by-同舟云学术

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release

Published:2024 Issue:4 Volume:15 Page:1324-1337
ISSN:2041-6520
Container-title:Chemical Science
language:en
Short-container-title:Chem. Sci.

Author:

Postupalenko Viktoriia¹^ORCID,Marx Léo²^ORCID,Pantin Mathilde²,Viertl David³⁴^ORCID,Gsponer Nadège¹^ORCID,Giudice Gaëlle¹,Gasilova Natalia⁵,Schottelius Margret³⁶^ORCID,Lévy Frédéric⁷,Garrouste Patrick²,Segura Jean-Manuel¹^ORCID,Nyanguile Origène¹^ORCID

Affiliation:

1. Institute of Life Technologies, HES-SO Valais-Wallis, Rue de l'Industrie 23, CH-1950 Sion, Switzerland

2. Debiopharm Research & Manufacturing SA, Campus “après-demain”, Rue du Levant 146, 1920 Martigny, Switzerland

3. Translational Radiopharmaceutical Sciences, Departments of Nuclear Medicine and of Oncology, CHUV/UNIL, 1011 Lausanne, Switzerland

4. In Vivo Imaging Facility, Department of Research and Training, University of Lausanne, CH-1011, Lausanne

5. EPFL Valais Wallis, MSEAP, ISIC-GE-VS, rue de l'Industrie 17, 1951 Sion, Switzerland

6. Agora, pôle de recherche sur le cancer, 1011 Lausanne, Switzerland

7. Debiopharm International SA, Forum “après-demain”, Chemin Messidor 5-7, Case postale 5911, 1002 Lausanne, Switzerland

Abstract

A one step template-directed method for site-specific conjugation of payloads to monoclonal antibodies is reported. Near 100% modification at a single lysine residue of the antibody Fc domain is achieved with a drug to antibody ratio of 2.

Funder

Innosuisse - Schweizerische Agentur für Innovationsförderung

Publisher

Royal Society of Chemistry (RSC)

Subject

General Chemistry

Link

http://pubs.rsc.org/en/content/articlepdf/2024/SC/D3SC04324J

Reference44 articles.

1. Template directed synthesis of antibody Fc conjugates with concomitant ligand release

2. Site-Specific Conjugation of Monomethyl Auristatin E to Anti-CD30 Antibodies Improves Their Pharmacokinetics and Therapeutic Index in Rodent Models

3. Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

4. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index

5. A Novel HER2-targeted Antibody–drug Conjugate Offers the Possibility of Clinical Dosing at Trastuzumab-equivalent Exposure Levels