Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody
ABSTRACTIMAB362/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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2255041 |
| _version_ | 1797367137823621120 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hayat Bähr-Mahmud |
| collection | DOAJ |
| description | ABSTRACTIMAB362/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). |
| first_indexed | 2024-03-08T17:13:05Z |
| format | Article |
| id | doaj.art-9d221a17a4384e5ba41b5f63a1b80c51 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T17:13:05Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-9d221a17a4384e5ba41b5f63a1b80c512024-01-03T19:25:37ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2255041Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibodyHayat Bähr-Mahmud0Ursula Ellinghaus1Christiane R. Stadler2Leyla Fischer3Claudia Lindemann4Anuhar Chaturvedi5Jan Diekmann6Stefan Wöll7Imke Biermann8Bernhard Hebich9Caroline Scharf10Manuela Siefke11Alexandra S. Roth12Martin Rao13Kerstin Brettschneider14Eva-Maria Ewen15Uğur Şahin16Özlem Türeci17BioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyBioNTech SE, Mainz, GermanyABSTRACTIMAB362/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).https://www.tandfonline.com/doi/10.1080/2162402X.2023.2255041ADCCBNT141human CLDN18.2IMAB362immunotherapyRiboMab |
| spellingShingle | 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 Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody OncoImmunology ADCC BNT141 human CLDN18.2 IMAB362 immunotherapy RiboMab |
| title | Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody |
| title_full | Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody |
| title_fullStr | Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody |
| title_full_unstemmed | Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody |
| title_short | Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody |
| title_sort | preclinical characterization of an mrna encoded anti claudin 18 2 antibody |
| topic | ADCC BNT141 human CLDN18.2 IMAB362 immunotherapy RiboMab |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2255041 |
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