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Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody

Authors :
Hayat Bähr-Mahmud
Ursula Ellinghaus
Christiane R. Stadler
Leyla Fischer
Claudia Lindemann
Anuhar Chaturvedi
Jan Diekmann
Stefan Wöll
Imke Biermann
Bernhard Hebich
Caroline Scharf
Manuela Siefke
Alexandra S. Roth
Martin Rao
Kerstin Brettschneider
Eva-Maria Ewen
Uğur Şahin
Özlem Türeci
Source :
OncoImmunology, Vol 12, Iss 1 (2023)
Publication Year :
2023
Publisher :
Taylor & Francis Group, 2023.

Abstract

IMAB362/Zolbetuximab, a first-in-class IgG1 antibody directed against the cancer-associated gastric-lineage marker CLDN18.2, has recently been reported to have met its primary endpoint in two phase 3 trials as a first-line treatment in combination with standard of care chemotherapy in CLDN18.2-positive Her2 negative advanced gastric cancer. Here we characterize the preclinical pharmacology of BNT141, a nucleoside-modified RNA therapeutic encoding the sequence of IMAB362/Zolbetuximab, formulated in lipid nanoparticles (LNP) for liver uptake. We show that the mRNA-encoded antibody displays a stable pharmacokinetic profile in preclinical animal models, mediates CLDN18.2-restricted cytotoxicity comparable to IMAB362 recombinant protein and inhibits human tumor xenograft growth in immunocompromised mice. BNT141 administration did not perpetrate mortality, clinical signs of toxicity, or gastric pathology in animal studies. A phase 1/2 clinical trial with BNT141 mRNA-LNP has been initiated in advanced CLDN18.2-expressing solid cancers (NCT04683939).

Details

Language :
English
ISSN :
2162402X
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
OncoImmunology
Publication Type :
Academic Journal
Accession number :
edsdoj.9d221a17a4384e5ba41b5f63a1b80c51
Document Type :
article
Full Text :
https://doi.org/10.1080/2162402X.2023.2255041