Zeitschriftenaufsatz | 2025

Considerations for use of humanized IgG1/4 Gottingen minipigs in safety assessment of antibody-based therapeutics

Autor:in
Lyander, Anna; Hannibal, Tine Dahlbaek; Egli, Jerome; Gauthier, Beatrice; Krarup, Mikkel Lykke; Gallo, Daniela; Jensen, Andres Eskjaer; Van Cruchten, Steven; Bulera, Steven; Cornet, Miranda; Hammer, Sabine Elisabeth; Henry, David; Jacobsen, Bjoern; Kendrick, John; MADSEN, L; Mhedhbi, Sofiene; Oag, Steven; Pedersen, Henrik Duelund; Teti, Manuela; Singh, Pramila
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Hammer, Sabina
Journal
Regulatory Toxicology And Pharmacology
Schlagwörter
Keywords; Humanized Gottingen minipigs; Immunogenicity; Safety assessment; antibody therapeutics; 3Rs
Dokumenten­typ
Originalarbeit
ISSN/eISSN
0273-2300 - 1096-0295
DOI
Öffnen URL 10.1016/j.yrtph.2025.105855
WoS ID
Öffnen URL WOS:001499413400001
PubMed ID
Öffnen URL MEDLINE:40398719

Weitere Details

Band
161
Seiten­anzahl
5
At the 16th Minipig Research Forum (MRF) held on May 22-24th, 2024 in Amsterdam, The Netherlands, a breakout session was organized to discuss perspectives on the utility and limitations of humanized IgG1/4 Gottingen Minipigs (hGMPs) for safety assessment of therapeutic antibodies. The session was attended by representatives from pharmaceutical and biotech companies, contract research organizations and academia with shared interest in research models suitable for use with novel biotherapeutics. hGMPs have been genetically modified to carry a mini repertoire of human genes encoding the soluble forms of immunoglobulin heavy chains gamma 1 and gamma 4 and immunoglobulin light chain kappa. An initial characterization of hGMPs for the toxicological testing of IgG1/4-based antibody therapeutics was published in 2022 and found that these animals reflected human clinical immunogenicity of four therapeutic antibodies, suggesting they could be a potential alternative to non-human primates for safety assessment of such antibodies. However, additional background data and experience with a broader range of therapeutics is needed to understand how hGMPs can be integrated into the toxicological testing of antibody therapeutics. This commentary aims to highlight key discussion points from the breakout At the 16th Minipig Research Forum (MRF) held on May 22-24th, 2024 in Amsterdam, The Netherlands, a breakout session was organized to discuss perspectives on the utility and limitations of humanized IgG1/4 Göttingen Minipigs (hGMPs) for safety assessment of therapeutic antibodies. The session was attended by representatives from pharmaceutical and biotech companies, contract research organizations and academia with shared interest in research models suitable for use with novel biotherapeutics. hGMPs have been genetically modified to carry a mini repertoire of human genes encoding the soluble forms of immunoglobulin heavy chains γ1 and γ4 and immunoglobulin light chain κ. An initial characterization of hGMPs for the toxicological testing of IgG1/4-based antibody therapeutics was published in 2022 and found that these animals reflected human clinical immunogenicity of four therapeutic antibodies, suggesting they could be a potential alternative to non-human primates for safety assessment of such antibodies. However, additional background data and experience with a broader range of therapeutics is needed to understand how hGMPs can be integrated into the toxicological testing of antibody therapeutics. This commentary aims to highlight key discussion points from the breakout session, including identification of data gaps, ongoing characterization efforts, and considerations for the use of hGMPs for the safety assessment of antibody-based therapeutics.Copyright © 2025. Published by Elsevier Inc.

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