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Poster display session

2067 - Preclinical Characterization of IMAB362-vcMMAE, an Anti-CLDN18.2 Antibody–Drug Conjugate

Date

11 Sep 2017

Session

Poster display session

Topics

Clinical Research

Presenters

Maria Kreuzberg

Citation

Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367

Authors

M. Kreuzberg1, R. Mitnacht-Kraus2, U. Sahin3, Ö. Türeci2

Author affiliations

  • 1 Ganymed Pharmaceuticals, AG, 55131 - Mainz/DE
  • 2 Ganymed Pharmaceuticals, AG, Mainz/DE
  • 3 Translational Oncology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz/DE
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Resources

Abstract 2067

Background

Antibody–drug conjugates combine the specific targeting and antitumor activity of monoclonal antibodies with the potent cell killing activity of cytotoxic small molecule drugs. IMAB362 is a monoclonal antibody specific for the tight junction protein Claudin 18.2 (CLDN18.2). In normal tissue, CLDN18.2 is exclusively expressed in the gastric mucosa. In the context of malignant transformation, CLDN18.2 can be found in gastric tumors as well as tumors from organs that do not normally express CLDN18.2 (eg, pancreas). Preclinical characterization of IMAB362 conjugated to the antimitotic molecule, monomethyl auristatin E, with a valine–citrulline linker (IMAB362–vcMMAE) is presented here.

Methods

IMAB362–vcMMAE binding characteristics and internalization were assessed in CLDN18.2-expressing human cell lines. Cell viability and IMAB362–vcMMAE-mediated cytotoxic effects (direct and indirect [bystander]) were also assessed in CLDN18.2 in vitro models. Xenograft mouse models of pancreatic and gastric cancers were developed to assess the cytotoxic and antitumor effects of IMAB362–vcMMAE in vitro.

Results

IMAB362–vcMMAE showed a slightly decreased relative binding affinity on CLDN18.2-transfected cells and cells that endogenously express CLDN18.2 compared with unconjugated IMAB362. In cell lines that internalized IMAB362–vcMMAE, cell viability was reduced by 45–90%; EC50 negatively correlated with CLDN18.2 expression level, with the lowest EC50 being

Conclusions

IMAB362–vcMMAE is a highly specific and potent antibody-drug conjugate against in vivo and in vitro models of gastric and pancreatic cancers.

Clinical trial identification

Legal entity responsible for the study

Ganymed Pharamaceuticals AG, A company of Astellas Pharma, Inc

Funding

Ganymed Pharamaceuticals AG, A company of Astellas Pharma, Inc

Disclosure

M. Kreuzberg: Emplyee of Ganymed Pharamceuticals AG, a company of Astellas Pharma, Inc. R. Mitnacht-Kraus: Employee of Ganymed Pharmaceuticals AG, a company of Astellas Pharma, Inc. In addition, Dr. Mitnacht-Kraus has a patent P-24PCT issued, a patent P-33PCT issued, a patent P-34PCT issued, and a patent P-36PCT issued. U. Sahin: Stock option owner, ex-shareholder and cofounder of Ganymed Pharmaceuticals AG and Founder/CEO/shareholder of Biontech Holding outside the submitted work. Dr. Sahin has several patents issued to this work that have been acquired by Astellas. Ö. Türeci: Stock option owner, ex-shareholder, cofounder & CEO of Ganymed Pharmaceuticals AG, has received consultancy fees from Astellas, and has several patents issued to this work that have been acquired by Astellas.

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