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A humanized minipig model for the toxicological testing of therapeutic recombinant antibodies.

Nature biomedical engineering (2022-09-23)
Tatiana Flisikowska, Jerome Egli, Krzysztof Flisikowski, Marlene Stumbaum, Erich Küng, Martin Ebeling, Roland Schmucki, Guy Georges, Thomas Singer, Mayuko Kurome, Barbara Kessler, Valeri Zakhartchenko, Eckhard Wolf, Felix Weber, Angelika Schnieke, Antonio Iglesias
ZUSAMMENFASSUNG

The safety of most human recombinant proteins can be evaluated in transgenic mice tolerant to specific human proteins. However, owing to insufficient genetic diversity and to fundamental differences in immune mechanisms, small-animal models of human diseases are often unsuitable for immunogenicity testing and for predicting adverse outcomes in human patients. Most human therapeutic antibodies trigger xenogeneic responses in wild-type animals and thus rapid clearance of the drugs, which makes in vivo toxicological testing of human antibodies challenging. Here we report the generation of Göttingen minipigs carrying a mini-repertoire of human genes for the immunoglobulin heavy chains γ1 and γ4 and the immunoglobulin light chain κ. In line with observations in human patients, the genetically modified minipigs tolerated the clinically non-immunogenic IgG1κ-isotype monoclonal antibodies daratumumab and bevacizumab, and elicited antibodies against the checkpoint inhibitor atezolizumab and the engineered interleukin cergutuzumab amunaleukin. The humanized minipigs can facilitate the safety and efficacy testing of therapeutic antibodies.

MATERIALIEN
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Marke
Produktbeschreibung

Sigma-Aldrich
Anti-Human IgG (γ-chain specific), F(ab′)2 fragment antibody produced in goat, affinity isolated antibody, buffered aqueous solution