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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

1200 - Good tolerability and limited target-specific tissue distribution of an anti-L1CAM antibody administered to cynomolgus monkey indicates favorable safety profile of L1CAM-targeting therapies

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Jacques Gaudreault

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

J. Gaudreault1, A. Schmidt1, P. Altevogt2, G. Spohn1

Author affiliations

  • 1 Rd, Elthera AG, 8952 - Schlieren/CH
  • 2 Translational Immunology, DKFZ, 69120 - Heidelberg/DE
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Resources

Abstract 1200

Background

L1 cell adhesion molecule (L1CAM) is a ∼200 kDa transmembrane protein which is overexpressed in several tumor types. Its expression has been shown to be a predictor of poor outcome in several independent publications. Anti-L1CAM antibody therapy, is expected to lead to tumor regression through inhibition of tumor growth, inhibition of migration/cell adhesion, reversal of chemoresistance and cell killing via ADCC. In addition to tumors, L1CAM is expressed in a restricted set of healthy tissues, including the nervous system and kidney tubules. The current study was conducted to investigate the acute tolerability and tissue distribution of an antibody directed against L1CAM and inform about the potential target organs which might be affected by anti-L1 CAM therapy.

Methods

The acute tolerability and biodistribution of an antibody that binds with high affinity to cynomolgus monkey L1CAM was evaluated. The antibody was administered in two IV bolus injections of 20 mg/kg, 24 hours apart to a single cynomolgus monkey. Clinical signs were recorded and the animal was sacrificed 48 hours after administration of the second dose, followed by macropathological inspection and tissue collection. A second untreated control animal was used as control for subsequent analyses. Tissues from both animals were collected, paraffin-blocked, and the presence of tissue-bound anti-L1CAM antibody was detected by immunohistochemistry.

Results

Administration of the anti-L1CAM antibody was well tolerated with no signs of acute local or systemic intolerance observed. In cynomolgus monkey, specific binding was observed in kidney tubules and Kupffer’s cells of the liver, while no binding was observed in the central nervous system, peripheral nerves, or any other tissues.

Conclusions

Administration of L1CAM antibody was well tolerated and the observed tissue distribution was consistent with the known expression profile of L1CAM. These data support the safety of anti-L1CAM therapy using an antibody approach.

Clinical trial identification

Legal entity responsible for the study

Elthera AG.

Funding

Elthera AG.

Editorial Acknowledgement

Disclosure

J. Gaudreault, A. Schmidt, P. Altevogt, G. Spohn: Stock ownership: Elthera AG.

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