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